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Biomedicine & Pharmacotherapy 146 (2022) 112514
Contents lists available at ScienceDirect
Biomedicine & Pharmacotherapy

journal homepage: www.elsevier.com/locate/biopha
Review
Essential oils as anticancer agents: Potential role in malignancies, drug

delivery mechanisms, and immune system enhancement
Mansi Sharma a, 1, Kamaljit Grewal b, 1, Rupali Jandrotia b, Daizy Rani Batish b, *,
Harminder Pal Singh a, *, Ravinder Kumar Kohli b
a
Department of Environment Studies, Panjab University, Chandigarh 160 014, India
b
Department of Botany, Panjab University, Chandigarh 160 014, India
A R T I C L E I N F O A B S T R A C T
Keywords: Cancer retains a central place in fatality rates among the wide variety of diseases known world over, and the
Essential oils conventional synthetic medicaments, albeit used until now, produce numerous side effects. As a result, newer,
Anticancer activity better, and safer alternatives such as natural plant products, are gravely required. Essential oils (EOs) offer a
Anti-mutagenic activity
plethora of bioactivities including antibacterial, antiviral, antioxidant, and anticancer properties, therefore, the
Anti-proliferative activity
Aromatherapy
use of EOs in combination with synthetic drugs or aromatherapy continues to be popular in many settings. In
Drug delivery systems view of the paramount importance of EOs and their potential bioactivities, this review summarizes the current
knowledge on the interconnection between EOs and cancer treatment. In particular, the current review presents
an updated summary of the chemical composition of EOs, their current applications in cancer treatments based
on clinical studies, and the mechanism of action against the cancer cell lines. Similarly, an overview of using EOs
in aromatherapy and enhancing immunity during cancer treatment is provided. Further, this review focuses on
the recent technological advancements such as the loading of EOs using protein microspheres, ligands, or
nanoemulsions/nanoencapsulation, which offer multiple benefits in cancer treatment via site-specific and target-
oriented delivery of drugs. The continuing clinical studies of EOs implicate that their pharmacological appli
cations are a rewarding research area.
1. Introduction cervix, colorectal, lung, and thyroid cancers. In general, the develop
ment of cancer can be divided into three stages: (1) initiation, at which
1.1. A general overview of cancer the exposure to carcinogen initiates DNA damage and mutations at
cellular level due to the failure/error in DNA repair mechanisms; (2)
Cancer is a complex genetic disorder that catalyses the uncontrolled promotion, at which expansion of cells leads to hyper proliferation,
growth and spread of abnormal cells in body, leading to life-threatening modification, and inflammation of the cells/tissues; and (3) progression,
situations. Aging, differences in lifestyle, hormonal changes, and expo at which tumour formation occurs from pre-neoplastic cells by clonal
sure to environmental carcinogens represent major signalling cues expansion [3]. DNA damage causes genomic instability, which is a
driving the activation of cancer in humans [1]. As per statistics for the fundamental cause of cancer [4]. Although some of the conventional
year 2020, cancer ranks second among the leading causes of death methods like chemotherapy, radiation therapy, and surgery are effective
worldwide, with an estimated 9.6 million deaths in 2018 [2]. Globally, in cancer treatment; however, these have led to the major side effects
about 17 million people are diagnosed with cancer every year and this and toxicities [5]. Moreover, the increased drug resistance in cancer
scenario is projected to amplify drastically in the near future [2]. About cells as a result of drug inactivation, mutations or alteration in expres
36 types of cancer have already been identified in humans and a sion levels of enzymes such as kinases or topoisomerases, chromosomal
considerable relationship between gender and type of cancer has been changes, modifications in drug-activating signal transduction pathways,
observed. Men are typically more prone to colorectal, liver, lung, pros decreased drug accumulation as a result of increased efflux, reversal of
tate, and stomach cancers, whereas women suffer more with breast, drug-induced damage due to effective DNA repair, inhibition of
* Corresponding authors.
E-mail addresses: daizybatish@yahoo.com (D.R. Batish), hpsingh_01@yahoo.com (H.P. Singh).
1
Equal First/Principal authors.
https://doi.org/10.1016/j.biopha.2021.112514
Received 21 October 2021; Received in revised form 30 November 2021; Accepted 6 December 2021
Available online 25 December 2021
0753-3322/© 2021 Published by Elsevier Masson SAS. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).
M. Sharma et al. Biomedicine & Pharmacotherapy 146 (2022) 112514
apoptosis due to prolonged drug usage, changes in DNA including

methylation/acetylation/alkylation, minimizes the efficacy of synthetic
drugs [6]. Considering the lack of effective and safe approaches, the
development of novel and natural chemotherapeutic agents is gravely
required. In this regard, the pharmacological properties of certain EOs
make them the appealing “first-choice” for cancer suppression therapies
[3,7], [8,9].
1.2. Essential oils: Introduction, nature, and biological activities
The discovery of natural plant-based products is rightly recognized

as a milestone in the history of health care [10], and their introduction
into the market in combination with synthetic medicines has resolved
many health concerns [3,11]. As a result, the extraction of plant sec
ondary metabolites’ such as essential oils (EOs) through steam or Fig. 1. Year-wise distribution of research from 2011 to 2020 on the in vitro/in
hydro-distillation processes [12], has witnessed a significant progress vivo anticancer activity of various essential oils.
over the years. Stored in oil/resin ducts, glands or trichomes (glandular (Source: Scopus, 2021).
hairs) of plants [13,14], these EOs play important roles in defense
against external agents and participate in signal transduction pathways
[14,15]. Besides, myriads of biological and medicinal properties are
attributed to EOs, and their aromatic nature finds use in cosmetics,
perfumery, and as flavouring agents in food industry [16,17].
EOs are a complex mixture of various chemical compounds; pri
marily characterized by volatility, aroma, low molecular weight, and
density < 1 [18]. The diverse biological properties of EOs arise from the
differences in their chemical constitution and structure [19,20]. At
present, three main classes of EOs are identified, namely terpenes and
terpenoids (major contributors), phenolics, and aliphatic compounds
[21].
Although versatile pharmacological aspects of EOs (antioxidant,
antimicrobial, anti-diabetic activities, and preventive cardiovascular
activity) have been discussed in the literature [22,23], yet the attempts
to have a comprehensive review on the in vivo/in vitro anticancer ap
Fig. 2. Top 14 countries producing research documents on the in vitro/in vivo
plications of EOs, including cell target specificity and drug delivery anticancer activity of various essential oils.
systems are largely lacking. In addition, recent information on (Source: Scopus, 2021).
anticancer/antitumour/anti-proliferative activities of EOs along with
their advantages in efficient target-specific drug delivery (in form of “antiproliferative” OR “cytotoxic” were also used under the condition
nanoencapsulation/nanoemulsions) and use in combination with that a phrase related to anticancer properties of EOs was also present in
conventional chemotherapy drugs is not readily available in a single the title or abstract of the same document. The research was focused on
article. Therefore, in this review, we have compiled the information studies dealing only with the in vitro/in vivo anticancer activities of the
on various EOs tested for their cytotoxic/anti-mutagenic/anti- EOs in general. The analysis in Scopus was carried out for the last 10
proliferative/apoptotic activities, emerging technologies for the effi years (2011–2020) on 14th September 2021. The search results yielded
cient delivery of EOs in the target cells, and the role of aromatherapy via a total of 1122 publications during the period 2011–2020. Starting with
combination of EOs with synthetic drugs in reducing toxicity and side merely 44 papers on the topic in 2011, the research has taken a long leap
effects related to anticancer treatment. Furthermore, to evaluate the covering 230 research documents in the year 2020 (Fig. 1). With regards
research trends in this field, a bibliometric analysis (2011–2020) is to the country-wise research data, India ranked first with a total of 230
presented. The rationale for this review is to fill the necessary gaps in publications followed by China and Brazil with a count of 158 and 115
knowledge pertaining to the anticancer potential of EOs, which includes papers, respectively (Fig. 2). Among the journals, two significant ones
country-wise contribution of studies, publication of articles in different were ‘Molecules’ and ‘Industrial Crops and Products’ that produced
journals, year-wise trend in research on this topic, and pioneer authors maximum number of papers during these years (data not shown). Out of
working under this theme. The provided information could be exploited the total 1122 publications, the majority fell under the subject areas of
by researchers in enhancing the development of efficient and pharmacology, toxicology, and pharmaceutics (499), followed by
less/non-toxic anticancer drugs that can alleviate cancer and positively biochemistry, genetics and molecular biology (415), medicine (321),
affect human health in an eco-friendly manner. agricultural and biological sciences (265), and chemistry (265). Author-
wise analysis data indicated that Bezerra D.P., Maggi F., Sharifi-Rad J.,
2. Methodology: database used, and keywords searched for data Costa E.V., Salehi B., are the pioneers on the topic who contributed 14,
retrieval 14, 14, 12, and 11 papers, respectively. Among 1122 papers, ~68%
were research articles, whereas ~24% and 6% were review articles and
A systematic search was carried out using the ‘Scopus’ database to book chapters, respectively. Finally, the relevant research articles per
collect the relevant literature on a wide variety of essential oils in nature taining to the search query were manually selected after studying every
with special mention to their anticancer properties. A set of keywords article in detail.
were finalized, and the search queries were integrated or divided by
using “AND” and “OR” taken together with the keywords. To build a 3. Essential oils are cytotoxic in nature
valid search query that retrieves maximum documents with minimum
irrelevant results, the keywords used included “essential oils” AND Essential oils (EOs) induce programmed cell death of cancer cells via
“anticancer*” OR “antitumour*”. Other keywords including
2
Fig. 3. Schematic view of the possible mechanism of action of essential oils as antioxidant, anti-mutagenic, and anti-proliferative agents. Cyt: cytochrome; PARP:
Poly-ADP ribose polymerase; ROS: reactive oxygen species.
apoptosis, necrosis, arrest of cell cycle, and dysfunctioning of main cell phenoxy radicals are formed, which again combine with ROS to prevent
organelles. This is coordinated by an increase in membrane fluidity of any further oxidative damage [8] (Fig. 3). Another antioxidant mecha
the affected cell, reduced adenosine triphosphate (ATP) generation, nism induced by EOs involves the upregulation of antioxidant enzymes
alteration in pH gradient, and loss of mitochondrial potential, which are (e.g., superoxide dismutase, glutathione peroxidase, and catalase) and
the major precursors of cell death [14]. All the three major types of non-antioxidants (e.g., glutathione) [27]. For example, under in vivo
chemical constituents in EOs i.e., phenols, aldehydes, and alcohols, have conditions, increase in the activity of various antioxidant enzymes and
been proposed to carry out this function. For instance, plant isoprenoids oxidised glutathione by EO of Wedelia chinensis (Osbeck) Merr. provided
could possibly reduce the size of tumour cell in cancer patients [24]. protection against lung cancer in mice [27].
Likewise, the EO of Eucalyptus camaldulensis Dehnh. penetrated the
membrane of Caco-2 colorectal cancer cells and induced programmed 3.1.2. Anti-mutagenic activity
cell death via reduction in cell size, membrane damage, and fragmen EOs, which have been identified to exert anti-mutagenic effect, play
tation of nuclei [25]. Moreover, a link between type of organism (eu a primordial role in cancer prevention. Cancer can be inhibited by
karyotes versus prokaryotes) and lipophilic nature of EO components is preventing direct penetration of mutagens into the cell membrane [3],
indicative of the toxic potential of EOs. In eukaryotes, toxicity decreases inactivating the mutagens by direct scavenging, capturing the free
with increase in lipophilicity of components, while in prokaryotes, it radicals produced by mutagens, inhibiting the conversion of promuta
increases with increasing lipophilicity [24]. In general, the anticancer gens to mutagens by cytochrome P450 enzyme, enzymatic detoxifica
potential of EOs is largely ascribed to their antioxidant, anti-mutagenic, tion of mutagens, and effective error free DNA repair [3] (see Fig. 3).
and anti-proliferative properties. Increasing evidence from various studies highlights a strong link be
tween EOs and cancer prevention. In fact, mitochondrial damage and
3.1. A walk-on-the-wild-side: EOs as source of antioxidant, anti- apoptosis in Saccharomyces cerevisiae (yeast) were reduced by the
mutagenic, and anti-proliferative activities treatment of EOs [8]. EOs modulate the activity of phase I (cytochrome
P450) and phase II (glutathione-S-transferase; GST, uridine 5′ -diphos
3.1.1. Antioxidant activity pho-glucuronosyltransferase; UGT, quinone reductase; QR, and epoxide
Antioxidants are defined as compounds that can inhibit/retard the hydrolase; EH) enzymes, which are mainly involved in the detoxification
oxidation of free radicals, when utilized in small amounts. The antiox of mutagens [3,28,29]. For example, Frankincense EO and citral-rich
idant property is one of the key biological properties of EOs to deal with lemongrass EO induced the production of phase I and phase II drug
oxidative stress [26]. Under oxidation-prone conditions in eukaryotes, metabolizing enzymes (such as GST) and inhibited cell proliferation and
the mitochondrial DNA damage driven by reactive oxygen species (ROS) tumour growth [30,31].
such as hydroxyl radicals, superoxide anions, and hydrogen peroxide,
inhibits the electron transport chain, thus leading to ROS accumulation. 3.1.3. Anti-proliferative activity
When ROS combines with EO, a chain of events is initiated and reactive EOs can exert anti-proliferative effect through multiple mechanisms
3
Table 1
Representative list of plant essential oils (EO) and their major constituent(s) with potential implications in type and mechanism of cancer prevention.
Type of Type of cancer (s) Targeted cancer cell lines and In vitro / In Source of EO Major constituent (s) Reference
bioactivity prevented IC50/EC50/CD50 values vivo studies (Plant name, (s)
Plant family)
Cytotoxicity Breast cancer MCF-7: IC50 = 100.0 µg mL-1; In vitro Abies alba Mill. Cone oil: α-pinene, β-pinene, [35]
MDA-MB-231: IC50 (Pinaceae) limonene;
= 100.0 µg mL-1 Seed oil: α-pinene, limonene,
β-myrcene
Cytotoxicity Breast cancer MCF-7: IC50 = 100.0 µg mL-1; In vitro Abies koreana E.H. Cone oil: α-pinene, β-pinene, [35]
MDA-MB-231: IC50 Wilson limonene;
= 100.0 µg mL-1 (Pinaceae) Seed oil: camphene, α-pinene,
limonene, bornyl acetate
Cytotoxicity Human glioblastoma, T98G: IC50 = 15.4 µg mL-1; MDA- In vitro Afrostyrax 2,4,5,7-tetrathiaoctane, [36]
Human breast MB-231: IC50 = 10.9 µg mL-1; lepidophyllus 2,4,5,7,9-pentathiadecane,
adenocarcinoma, A375: IC50 = 20.6 µg mL-1; Mildbr. 6-methyl-2,4,5,7,9-pentathiadecane,
Human malignant HCT116: IC50 = 12.4 µg mL-1 (Huaceae) 2,3,5-trithiahexane
melanoma,
Human colon
carcinoma
Anti- Prostate cancer, LNCaP: IC50 = 0.35 mg mL-1; PC- In vitro Ageratum conyzoides Precocene, caryophyllene, [21]
proliferative Human glioblastoma 3: IC50 = 0.49 mg mL-1; SF-763: (L.) L. β-sesquiphellandrene, germacrene D
IC50 = 0.38 mg mL-1; SF-767: IC50 (Asteraceae)
= 0.43 mg mL-1
Apoptosis Human HL-60 In vitro Allium sativum L. Diallyl disulfide (DADS), Diallyl [37]
promyelocytic trisulfide (DATriS)
leukemia
Cytotoxicity Human epidermoid A431 and HaCaT: < 20% viable In vitro Aniba rosaeodora Linalool [38]
carcinoma cells at 400 nL mL-1 EO after 4 h Ducke
incubation; < 50% viable cells at (Lauraceae)
300 nL mL-1 EO after incubation
for 12 h
Anti tumour Colorectal cancer HCT 116: decrease in tumour size In vivo (in Aquilaria crassna Benzylacetone, neopetasane, n- [39],[40]
after 8 weeks (0.37–0.24% athymic NCR Pierre ex Lecomte hexadecanoic acid,
inhibition at 100–200 mg kg-1 nu/nu nude (Thymelaeaceae) the dihydroagarofuran aldehyde
EO); decrease in apoptosis and mice) (1 S,2 S,6 S,9 R)− 6,
necrosis 10,10-trimethyl-11-oxatricyclo
[7.2.1.01,6]dodecane-2-
carbaldehyde, valerianol,
dihydrokaranone, jinko-eremol,
β-eudesmol [40]
Cytotoxicity Human colon HT-29: GI50 = 46.82 µg mL-1 In vitro Artemisia campestris β-pinene, limonene, germacrene D, c- [41]
carcinoma L. terpinene, β-myrcene, α-pinene, (Z)-
(Asteraceae) β-ocimene, (E)-β-ocimene,
β-eudesmol, p-cymene
Cytotoxicity Murine mastocytoma, Leaf EO: P815: IC50 = 15.0 µg mL- In vitro Artemisia herba-alba Leaf EO: 2,5-octadecadiynoic acid, [42]
1
Hamster kidney ; BSR: IC50 = 26.0 µg mL-1; Asso methyl ester,
carcinoma Capitulum EO: P815: IC50 (Asteraceae) α-bulnesene, widdrene, eucalyptol
= 36.0 µg mL-1; BSR: IC50 (1,8-cineole), bisabolone oxide;
= 20.0 µg mL-1 Capitulum EO: β-guaiene,
2,5-octadecadiynoic acid, methyl
ester, bisabolone oxide,
β-thujone, verbenol,
(+) 2,3,6,7-tetramethyl-,
4,4aα,5,8,8aβ,9β,9aα,10,10aα-
decahydroanthracen-9-ol
Cytotoxicity Colon cancer, Caco-2: IC50 = 19.5 µg mL-1; A- In vitro Artemisia indica Artemisia ketone, [43]
Liver cancer, 549: IC50 = 25 µg mL-1; HEP-2: Willd. germacrene B, borneol, chrysanthenyl
Lung cancer, IC50 = 15.5 µg mL-1; THP-1: IC50 (Asteraceae) acetate, p-cymene, α-thujone,
Leukemia = 10 µg mL-1 β-pinene
Anti- Human breast MDA-MB-231: IC50 = 51.7 µg mL- In vitro Athanasia brownii Selin-11-en-4-α-ol, caryophyllene [44]
1
proliferative adenocarcinoma, ; A375: IC50 = 19.9 µg mL-1; Hochr. oxide, humulene epoxide II, (E)-
Human malignant HCT116: IC50 = 29.53 µg mL-1 (Asteraceae) nerolidol
melanoma, Human
colon carcinoma
Apoptosis Breast cancer T47D: IC50 = 1:900 and 1:1450; In vitro Boswellia sacra α-pinene, α-thujene, β-pinene, [45]
MCF-7: IC50 = 1:1000 and Flueck. myrcene, boswellic acid
1:1800; MDA-MB-231: IC50 (Burseraceae)
= 1:950 and 1:1300 at 78 ◦ C and
100 ◦ C, respectively
Anti-tumour; Human pancreatic Fraction I EO: MIA Paca-2: IC50 In vivo Boswellia sacra α-thujene, β-pinene, myrcene, [46]
apoptosis cancer = 1:440; Panc-28: IC50 = 1:440; Flueck. α-pinene, boswellic acid, limonene;
DANG: IC50 = 1:570; (Burseraceae) Fraction III EO: borneol, dimethyl
Fraction II EO: MIA Paca-2: IC50 ether orcinol, allo-aromadendrene,
= 1:590; Panc-28: IC50 = 1:700; γ-cadinene, caryophyllene oxide
(continued on next page)
4
Table 1 (continued )
Plant family)
DANG: IC50 = 1:720;

Fraction III EO: MIA Paca-2: IC50
= 1:860; Panc-28: IC50 = 1:930;
DANG: IC50 = 1:950;
Fraction IV EO: MIA Paca-2: IC50
= 1:1230; Panc-28: IC50
= 1:1560; DANG: IC50 = 1:1350;
decrease in tumour volume after
EO administration
(124.10–66.54 mm3 and
239.32–56.78 mm3 after second
and third dose of EO injection,
respectively)
Anti- Human prostate PC-3: IC50 = 15.2 – 54.9 µg mL-1; In vitro Bursera glabrifolia α-terpineol, [47]
proliferative cancer, OVCAR-3: IC50 = 27.3 – (Kunth) Engl. α-terpinene, limonene,
Human ovarian 53.7 µg mL-1; K-562: IC50 = 32.4 – (Burseraceae) β-pinene
carcinoma, 75.9 µg mL-1
Myelogenous
leukemia
Cytotoxicity Murine melanoma, B16F10-Nex2: IC50 = 61.5 µg mL- In vitro Casearia sylvestris α-zingiberene, E-caryophyllene, [48]
1
Human melanoma, ; A2058: IC50 = 41.1 µg mL-1; Sw. γ-muurolene, acoradiene,
Glioblastoma, U87: IC50 = 27.1 µg mL-1; HL-60: (Salicaceae/ viridiflorene
Leukemia, IC50 = 12.0 µg mL-1; Siha: IC50 Flacourtiaceae)
Uterus carcinoma, = 23.9 µg mL-1; MCF-7: IC50
Breast cancer, = 42.2 µg mL-1; HeLa: IC50
Human cervical = 29.0 µg mL-1
carcinoma
Cytotoxicity Human breast cancer MCF-7: IC50 = 21.5 mg L-1 In vitro Cedrelopsis grevei (E)-β-farnesene, δ-cadinene, [49]
Baill. & Courchet α-copaene, β-elemene
(Rutaceae)
Cytotoxicity Human chronic K562: IC50 = 59.37 µg mL-1 In vitro Cedrus atlantica α-pinene, himachalene, [50],[51]
myelogenous (Endl.) Manetti ex β-himachalene, cis-α-atlantone,
leukemia Carrière himachalol, germacrene D,
(Pinaceae) β-copaene [51]
Cytotoxicity Human chronic K562: IC50 = 37.09 µg mL-1 In vitro Cedrus deodara Leaf oil: benzaldehyde, [50],[51]
myelogenous (Roxb. ex D.Don) G. β-caryophyllene, germacrene D,
leukemia Don myrcene, β-pinene,
(Pinaceae) α-pinene, l-Δ3-carene, borneol; Wood
oil: α -himachalene,
β-himachalene, himachalol,
allohimachalol,
(+)-longborenol, atlantone (mainly
trans-isomer), p-methyl
acetophenone, eodarone [51]
Cytotoxicity Human chronic K562: IC50 = 23.38 µg mL-1 In vitro Cedrus libani A. Germacrene D, [50],[51]
myelogenous Rich. β-caryophyllene, γ-cadinene, trans-
leukemia (Pinaceae) α-bisabolene,
γ-muurolen, 4(14)-salvialen-1-one
[51]
Cytotoxicity Acute lymphoblastic CCRF-CEM: IC50 = 38.62 µg mL-1; In vitro Cedrus libani A. β-himachalene, α-himachalene, [52]
leukemia CEM/ADR5000: IC50 Rich. γ-himachalene, α-(E)-atlantone,
= 35.12 µg mL-1 (Pinaceae) himachalol, allohimachalol, γ-(Z)-
atlantone, α-(Z)-atlantone
Cytotoxicity Human colorectal Lim1863: IC50 In vitro Citrus aurantium L. Limonene, α-pinene, [53]
carcinoma = 2.18–2.44 µL mL-1 subsp. amara β-myrcene
(Link.) Engl.
(Rutaceae)
Cell death Human SH-SY5Y: ~20% viability at In vitro Citrus bergamia Limonene, linalyl acetate, linalool, [54]
neuroblastoma 0.01% EO after 72 h Risso & Poit. β-pinene, γ-terpinene
(Rutaceae)
Anti- Human HepG2: EC50 = 0.091 mg mL-1; In vitro Citrus medica L. Limonene, myrcene, geraniol, nerol [55]
proliferative; hepatocellular MCF-7: EC50 = 0.16 mg mL-1; (Rutaceae)
Cytotoxicity carcinoma, Caco2: EC50 = 0.013 mg mL-1;
Breast THP-1: EC50 = 0.074 mg mL-1;
adenocarcinoma, A375: EC50 = 0.0057 mg mL-1
Colon
adenocarcinoma,
Monocytic leukemia,
Malignant melanoma
Anti- Mouse lymphoma, BS-241: IC50 = 0.3125 µL mL-1 at In vitro Commiphora Germacrene D, α-pinene, sabinene, [56]
proliferative Epstein-Barr virus- 24 h; 1:5000 EO dilution (87% gileadensis (L.) C. β-caryophyllene
transformed human B cells dead); MoFir: IC50 Chr.
lymphocytes = 2.5 µL mL-1 at 24 h; 1:5000 EO (Burseraceae)
dilution (40% cells dead)
5
Plant family)
Anti- Human In vitro: decrease in cell viability In vitro Cupressus α-pinene, δ-3-carene, α-cedrol, [57]
proliferative; promyelocytic with increasing EO concentrations In vivo (in sempervirens L. α-terpinolene, limonene
Antitumour leukemia, (100–500 µg mL-1): HL-60: female Swiss (Cupressaceae)
Ehrlich ascites 21.33–66.78%; NB4: albino mice)
carcinoma 19.40–73.23%; EACC:
11.30–58.77%; HL-60: LC50
= 365.41 µg mL-1; NB4: LC50
= 333.79 µg mL-1; EACC: LC50
= 372.43 µg mL-1;
In vivo: increase in mice survival
days (29.83 days during pre-
initiation EO treatment)
Cytotoxicity Prostate cancer, LNCaP: IC50 In vitro Curcuma aromatica 8,9-dehydro-9-formyl- [58]
Melanoma = 123.43–259.62 µg mL-1; B16: Salisb. cycloisolongifolene, germacrone, ar-
IC50 = 30.66–169.60 µg mL-1 (Zingiberaceae) turmerone, turmerone, ermanthin,
β-sesquiphyllandrene,
ar-curcumene
Cytotoxicity; Non-small cell lung CAEO (at 24, 48, and 72 h In vivo Curcuma aromatica Zingiberene, [59]
Antitumour; cancer treatment, respectively): A549: Salisb. β-sesquiphellandrene, turmerone
Apoptosis; IC50 = 190.0, 95.0, and (Zingiberaceae)
Cell death 90.0 µg mL-1; NCI-H23: IC50
= 160.0, 155.0, and 145.0 µg mL-
1
; NCI-H1299: IC50 = 160.0,
100.0, and 60.0 µg mL-1;
CSEO: A549: IC50 = 300.0 µg mL-
1
at 72 h; NCI-H23: IC50 not
obtained; NCI-H1299: IC50
= 300.0 and 120.0 µg mL-1 at 48
and 72 h, respectively; increased
apoptosis in NCI-H1299 cells
(~30.7% after 72 h EO treatment)
Cytotoxicity Dalton’s lymphoma In vitro: DLA: IC50 = 8.0 µg; EAC: In vitro Curcuma longa L. α-turmerone, β-turmerone, [60],[61]
ascites, IC50 = 18.0 µg; In vivo (in (Zingiberaceae) ar-turmerone, α-phellandrene, 1,8-
Ehrlich ascites In vivo: DLA: increase in mice mice) cineole [61]
carcinoma survival (56.25%) and reduction
in tumour size
Anti- Mouse melanoma, In vitro: B16BL6: IC50 In vitro Curcuma zedoaria Curzerenone, germacrone, camphor [62],[63]
proliferative Human hepatoma = 41.8 µg mL-1; SMMC-7721: IC50 In vivo (in (Christm.) Roscoe [63]
= 30.7 µg mL-1; C57BL/6 mice (Zingiberaceae)
In vivo: inhibition of tumour at and Sprague-
100 and 200 mg kg-1 day-1 EO for Dawley rats)
28 days; decrease in tumour
weight (4.34 g in control,
2.92–2.48 g at 100 and mg kg-1
day-1 EO, respectively)
Cytotoxicity; Non-small cell lung In vitro (at 24–72 h EO treatment): In vitro Curcuma zedoaria 8,9-dehydro-9-formyl- [64]
Apoptosis carcinoma H1299: IC50 = 80–170 µg mL-1; In vivo [in male (Christm.) Roscoe cycloisolongifolene, 6-ethenyl-
A549: IC50 = 80–250 µg mL-1; BALB/c (nu/ (Zingiberaceae) 4,5,6,7-tetrahydro-3,6-dimethyl-5-
H23: IC50 = 180–185 µg mL-1; nu) nude mice] isopropenyl-trans-benzofuran,
H1299 (110 µg mL-1 EO at 24, 48, eucalyptol, γ-elemene
and 72 h): apoptosis induction
(41.6% after 72 h);
In vivo: dose-dependent decrease
in tumour volume and weight
upon EO treatment (5 times a
week; 2.5–240 mg kg-1 EO)
Anti- Prostate cancer, LNCaP: IC50 = 6.36 µg mL-1; PC- In vitro Cymbopogon citratus Geranial/citral A, [65]
proliferative Glioblastoma 3: IC50 = 32.1 µg mL-1; SF-767: (DC.) Stapf neral/citral B, myrcene
IC50 = 45.13 µg mL-1; SF-763: (Poaceae)
IC50 = 172.05 µg mL-1
Anti- Prostate cancer, LNCaP: IC50 = 160.1 µg mL-1; PC- In vitro Cymbopogon Limonene, mentha-1(7), 8-dien-2-ol [65]
proliferative Glioblastoma 3: IC50 = 303.3 µg mL-1; SF-767: giganteus Chiov. cis, mentha-1(7),8-dien-2-ol trans,
IC50 = 255.1 µg mL-1; SF-763: (Poaceae) mentha-2,8-diene-1-ol trans-para,
IC50 = 217.0 µg mL-1 mentha-2,8-diene-1-ol cis-para
Cytotoxicity Breast cancer MDA-MB-231: decrease in In vitro Cyperus articulatus Sesquiterpenes, monoterpenes, [66]
viability of cells at high doses of L. nootkatone, 6-methyl-3,5-heptadien-
EO after 48 h (Cyperaceae) 2-one, retinene, nopinone,
cycloeucalenol, anozol, toosendanin,
furanone, ethanone, vitamin A
Cytotoxicity Human glioblastoma, U-138 MG: 35.0% at 500 µg mL-1 In vitro Drimys angustifolia Monoterpenoids, sesquiterpenoids, [67]
Human bladder EO; Miers bicyclogermacrene, sabinene, mircene
carcinoma T24: 36.7% and 73.7% at 250 and (Winteraceae)
500 µg mL-1 EO, respectively
Cytotoxicity In vitro [67]
6
Plant family)
Human glioblastoma, U-138 MG: 42.5% and 67.8% at Drimys brasiliensis Sesquiterpenoids, monoterpenoids,
Human bladder 250 and 500 µg mL-1 EO; Miers cyclocolorenone, terpinen-4-ol,
carcinoma T24: 33.2%, 60.3%, and 80.5% at (Winteraceae) α-gurjunene
150, 250, and 500 µg mL-1 EO,
respectively
Cytotoxicity; Mouse melanoma, In vitro: B16-F10: IC50 In vitro Duguetia β-bisabolene, elemicin, germacrene D, [68]
Antitumour Human = 16.89 µg mL-1; HepG2: IC50 In vivo (in male gardneriana Mart. cyperene
hepatocellular = 19.16 µg mL-1; HL-60: IC50 C57BL/6 mice) (Annonaceae)
carcinoma, = 13.08 µg mL-1; K562: IC50
Human chronic = 19.33 µg mL-1;
myelocytic leukemia, In vivo: inhibition of tumour
Human growth (5.37 – 37.52%) at 40 and
promyelocytic 80 mg kg-1 day-1
leukemia
Cytotoxicity Hepatocellular HepG2: IC50 = 25.6 µM In vitro Erigeron bonariensis o-ocimene, trans-α-farnesene, [69]
carcinoma L. isolongifolene-5-ol,
(Asteraceae) α-maaliene, berkheyaradulen,
α-muurolene, ledene oxide-(i)
Cytotoxicity Colorectal cancer Caco-2: IC50 = 100 µg mL-1 after In vitro Eucalyptus 1,8-cineole, α-pinene, p-cymene, [25]
EO treatment for 72 h camaldulensis α-phellandrene, c-terpinene, limonene
Dehnh.
(Myrtaceae)
Cytotoxicity Lung cancer A549: decrease in % cell survival In vitro Eucalyptus globulus 1,8-cineole, citronellal, citronellol, [70]
with increasing concentrations of Labill. citronellyl acetate, p-cymene,
EO (20%, 40%, 60%, 80%, and (Myrtaceae) eucamalol, limonene, linalool,
100%) β-pinene,
γ-terpinene,
α-terpineol, alloocimene,
aromadendrene
Anti- Hepatocellular In vitro (after 48 h EO treatment): In vitro Eupatorium Torreyol, aristolone, [71]
proliferative; carcinoma HepG2: IC50 = 17.74 µg mL-1; In vivo (in adenophorum α-bisabolol, α-curcumene, palmitic
Antitumour; Hep3B: IC50 = 49.56 µg mL-1; HepG2-bearing Spreng. acid, β-bisabolene,
Apoptosis SMMC-7721: IC50 = 39.20 µg mL- nude mouse) (Asteraceae) β-sesquiphellandrene
1
;
In vivo (at 30 – 120 mg kg-1 2
days-1 EO): inhibition of tumour
growth; decrease in tumour
weight, increase in apoptotic cells
Cytotoxicity Gastric AGS: decrease in tumour In vitro Ferula assa-foetida α-D-xylofuranoside, methyl 2,5-di-O- [72]
adenocarcinoma proliferation after 24, 48, and L. methyl, E-1-propenyl sec-butyl
72 h EO treatment at (Apiaceae) disulfide, Z-1-propenyl sec-butyl
0.01–10 µL mL-1 disulfide
Anti- Colon HepG2: EC50 = no activity; In vitro Fortunella margarita Limonene, myrcene, [73]
proliferative adenocarcinoma, Caco2: EC50 = 0.1 µg mL-1; MCF- (Lour.) Swingle δ-germacrene
Leukemia 7: EC50 = no activity; THP-1: EC50 (Rutaceae)
= 0.1 µg mL-1
Cytotoxicity Breast cancer Leaf oil: MCF-7: > 50% cell died In vitro Garcinia atroviridis Stem bark oil: palmitoleic acid, [74]
(and cell viability = 16%) at the Griff. ex T.Anderson palmitic acid;
highest EO concentration (Clusiaceae) Leaf oil: (E)-β-farnesene,
(100 µg mL-1 at 24 h); IC50 β-caryophyllene
= 71.0 µg mL-1
Anti- Breast cancer MCF-7: IC50 = 45.2 µg mL-1 In vitro Garcinia celebica L. α-copaene, germacrene D, [75]
proliferative (decrease in cell viability by 2.8%, (Clusiaceae) β-caryophyllene
2.8%, and 3.0% after 24, 48, and
72 h treatment with EO at
100 µg mL-1)
Cell growth Hepatocellular HA22T/VGH: IC50 = 60.5 µg mL- In vitro Glandora m-camphorene, heptacosane, [76]
1
inhibition carcinoma, ; HepG2: IC50 = 65.0 µg mL-1; rosmarinifolia (Ten.) nonacosane, hydroxy-methyl-
Breast cancer Hep3B: IC50 = 61.0 µg mL-1; SUM D.C. Thomas naphthoquinone, 2,6-dimethyl-10-(p-
149: IC50 = 65.0 µg mL-1; MDA- (Boraginaceae) tolyl)− 2,6-(E)-undecadiene,
MB-231: IC50 = 46.5 µg mL-1 cembrene C, phytol
Cytotoxicity; Colon cancer, In vitro: HCT-8: IC50 = 1.7 µg mL- In vitro Guatteria friesiana β-eudesmol, γ-eudesmol, [77]
1
Antitumour Leukemia, ; HL-60: IC50 = 9.4 µg mL-1; SF- In vivo (in male (W.A.Rodrigues) α-eudesmol, spathulenol, elemol, 10-
Brain cancer, 295: IC50 = 6.7 µg mL-1, MDA- Swiss mice) Erkens & Maas epi-γ-eudesmol, hinesol, carissone
Melanoma MB-435: IC50 = 9.4 µg mL-1 (Annonaceae)
In vivo: Sarcoma-180:
Intraperitoneal EO (50 and
100 mg kg-1 day-1): 43.4–54.2%
tumour growth inhibition;
Oral EO (100 and 200 mg kg-1
day-1): 6.6–42.8% tumour growth
inhibition
Cytotoxicity; Ovarian In vitro: OVCAR-8: IC50 In vitro γ-patchoulene, [78]
Antitumour adenocarcinoma, = 20.8 µg mL-1; NCI-H358M: IC50 In vivo (in mice (E)-caryophyllene,
7
Plant family)
Bronchoalveolar lung = 3.8 µg mL-1; PC-3 M: IC50 transplanted Guatteria pogonopus β-pinene,
carcinoma, = 17.0 µg mL-1; with tumour Mart. germacrene D, bicyclogermacrene,
Metastatic prostate In vivo: inhibition of Sarcoma 180 cells) (Annonaceae) α-pinene, germacrene B
carcinoma tumour growth by 25.3% and
42.6% at 50 and 100 mg kg-1 day-
1
Cytotoxicity Breast cancer MCF-7: IC50 = 16.0 mg L-1 In vitro Helichrysum 1,8-cineole, p-cymene, (E)-β-ocimene, [79]
gymnocephalum 2,3-dihydro-1,8-cineole,
(DC.) Humbert α-terpinolene,
(Asteraceae) bicyclosesquiphellandrene,
γ-curcumene, α-amorphene,
bicyclogermacrene
Cytotoxicity Breast cancer, 22EO: MCF-7: IC50 In vitro Iryanthera polyneura Spathulenol, [80]
Prostate cancer = 22.28 µg mL-1; 80EO: MCF-7: Ducke α-cadinol,
IC50 = 22.90 µg mL-1; 530EO: (Myristicaceae) τ-muurolol,
MCF-7: IC50 = 28.43 µg mL-1; terpenes (τ-muurolene, α-muurolene,
22EO: PC-3: IC50 = 14.69 µg mL- elemol, Ses4, Ses5)
1
; 80EO: IC50 = 13.63 µg mL-1;
530EO: IC50 = 12.48 µg mL-1
Cytotoxicity Acute lymphoblastic CCRF-CEM: IC50 = 41.50 µg mL-1; In vitro Juniperus excela M. α-pinene, cedrol, δ-3-carene, [52]
leukemia CEM/ADR5000: IC50 Bieb. limonene, terpinolene, myrcene
= 44.85 µg mL− 1 (Cupressaceae)
Cytotoxicity Acute lymphoblastic CCRF-CEM: IC50 = 29.46 µg mL-1; In vitro Juniperus oxycedrus cis-calamenene, cuparene, [52]
leukemia CEM/ADR5000: IC50 L. cis-thujopsenal, cis-thujopsene,
= 32.85 µg mL-1 (Cupressaceae) δ-cadinene, cedrol, 1-epi-cubenol,
cubenol, α-muurolol
Anti- Human prostate In vitro: PC-3: 0.037%; DU145: In vitro Lavandula Linalool, linalyl acetate [81]
proliferative; cancer 0.199%; In vivo (in male angustifolia Mill.
Apoptosis; In vivo: mild heart edema upon EO nude mice) (Lamiaceae)
Cell cycle treatment at 200 mg kg-1 body
arrest weight and suppression of tumour
growth
Cytotoxicity Human cervix HeLa: IC50 = 80.62 µg mL-1; In vitro Lavandula Linalool, borneol, linalyl acetate [82]
carcinoma, A549: IC50 = 88.90 µg mL-1 angustifolia Mill.
Lung (Lamiaceae)
adenocarcinoma
Anti- Squamous cell UMSCC1: IC50 = 292.6 µg mL-1 In vitro Levisticum officinale α-terpinyl acetate, [83]
proliferative carcinoma W.D.J.Koch β-phellandrene, β-myrcene, ligustilide
(Apiaceae)
Apoptosis Human myeloid HL-60: cell viability reduced after In vitro Lindera umbellata Terpenes, alcohol esters, linalool, [84]
leukemia 48 h EO treatment at 5 or Thunb. geranyl acetate, limonene, α-pinene,
50 µg mL-1 (Lauraceae) geraniol, cineol
Cytotoxicity; Human In vitro: HepG2: IC50 In vitro Lippia gracilis Thymol, p-cymene, thymol methyl [85]
Antitumour hepatocellular = 4.93 µg mL-1; K562: IC50 In vivo (in male Schauer ether, γ-terpinene, myrcene, thymol
carcinoma, = 22.92 µg mL-1; B16-F10: IC50 Swiss mice) (Verbenaceae) acetate
Human chronic = 7.01 µg mL-1;
myelocytic leukemia, In vivo: Sarcoma 180: 38.5–41.9%
Mouse melanoma tumour growth inhibition upon
treatment with EO at 40 and
80 mg kg-1 day-1
Anti- Prostate cancer, LNCaP: IC50 = 0.58 mg mL-1; PC- In vitro Lippia multiflora p-cymene, γ-terpinene, [21]
proliferative Human glioblastoma 3: IC50 = 0.30 mg mL-1; SF-763: Moldenke thymyle acetate,
IC50 = 0.47 mg mL-1; SF-767: IC50 (Verbenaceae) β-caryophyllene, thymol, eucalyptol,
= 0.31 mg mL-1 α-phellandrene,
α-thujene, myrcene, germacrene D,
α-terpinene, α-humulene, carvacrol,
caryophyllene oxide, (E)-β-ocimene,
elemol, limonene
Cytotoxicity Cervical cancer, Leaf oil: HeLa: IC50 In vitro Liquidambar Leaf oil: d-limonene, α-pinene, [86]
Breast cancer, = 136.27 µg mL-1; MCF-7: IC50 styraciflua L. β-pinene;
Hepatic cancer = 234.0 µg mL-1; HepG-2: IC50 (Altingiaceae) Stem oil: germacrene D,
= 157.6 µg mL-1; β-caryophyllene,
Stem oil: HeLa: IC50 α-cadinol, d-limonene,
= 119.78 µg mL-1; MCF-7: IC50 α-pinene, β-pinene
= 172.2 µg mL-1; HepG-2: IC50
= 136.9 µg mL-1
Anti- Human colon Leaf oil: HCT116: IC50 In vitro Liriodendron Leaf/Flower oil: germacrene D, [87]
proliferative carcinoma, = 6.11 µg mL-1; MDA-MB-231: tulipifera L. β-elemene, (E)-nerolidol, (Z)-
Human breast IC50 = 3.40 µg mL-1; T98G: IC50 (Magnoliaceae) β-ocimene, (E)-β-ocimene,
adenocarcinoma, = 3.23 µg mL-1; A375: IC50 bicyclogermacrene,
Human glioblastoma = 3.22 µg mL-1; δ-cadinene, bornyl acetate, (E)-
multiforme, Flower oil: HCT116: IC50 caryophyllene, α-cadinol, epi-
Human melanoma = 6.78 µg mL-1; MDA-MB-231: α-muurolol;
IC50 = 7.55 µg mL-1; T98G: IC50 Fruit oil: (Z)-β-ocimene, (E)-
8
Plant family)
= 2.5 µg mL-1; A375: IC50 β-ocimene, bornyl acetate,

= 12.83 µg mL-1 germacrene D, β-elemene, (E)-
nerolidol, borneol, α-cadinol, selin-
11-en-4-α-ol, epi-α-muurolol, linalool
Apoptosis; Cell Non-small cell lung A549: decrease in survivability of In vitro Litsea cubeba (Lour.) Seed oil: citronellal, neo-isopulegol, [33]
cycle arrest carcinoma cells with increasing time Pers. isopulegol, citronellol
exposure (24, 48, and 72 h EO (Lauraceae)
treatment); increase in %
apoptotic cells after 12, 24, and
36 h EO treatment
Cytotoxicity Glioma, Human lung % Growth inhibition In vitro Malus domestica Eucalyptol, phytol, α-farnesene, [88]
carcinoma, (100–2000 µg mL-1 EO Borkh. pentacosane
Ovarian cancer, treatment): C-6: 5.5–98.2%; (Rosaceae)
Human acute A549: 11.5–76.7%; CHOK1:
monocytic leukemia 13.5–69.5% (300–2000 µg mL-1
EO treatment); THP-1:
19.9–65.7% (300–1000 µg mL-1
EO treatment)
Cytotoxicity Human breast cancer MCF-7: IC50 = 12.0 mg L-1 In vitro Melaleuca armillaris 1,8-cineole, camphene, [89]
(Sol. ex Gaertn.) α-pinene, sabinene
Sm.
(Myrtaceae)
Apoptosis Glioblastoma A172 and U87: decrease in cell In vitro Melissa officinalis L. Citral, neral, geranial [90]
viability with increasing EO (Lamiaceae)
concentrations (4.6–36.8 µg mL-
1
) for 48 h;
A172: increase in the number of
apoptotic cells upon treatment
with 36.8 µg mL-1 EO for 24 h
Cytotoxicity Human cervix HeLa: IC50 = 165.24 µg mL-1; In vitro Mentha piperita L. Menthol, menthone, 1,8-cineol, [82]
carcinoma, A549: IC50 = 183.0 µg mL-1 (after (Lamiaceae) menthyl acetate
Lung 48 h EO treatment)
adenocarcinoma
Cytotoxicity Human cervix HeLa: IC50 = 168.58 µg mL-1; In vitro Mentha pulegium L. Pulegone, piperitone, trans-isocitral, [82]
carcinoma, A549: IC50 = 253.64 µg mL-1 (Lamiaceae) limonene
Lung (after 48 h EO treatment)
adenocarcinoma
Anti- Human HepG2: EC50 = 0.22 µg mL-1; In vitro Mentha spicata L. Carvone, limonene, β-pinene [73]
proliferative hepatocellular Caco2: EC50 = 0.162 µg mL-1; (Lamiaceae)
carcinoma, MCF-7: EC50 = 0.284 µg mL-1;
Colon THP-1: EC50 = 0.71 µg mL-1
adenocarcinoma,
Breast
adenocarcinoma,
Leukemia
Cytotoxicity; Ovarian In vitro: OVCAR-8: IC50 In vitro Mentha villosa Huds. Rotundifolone, limonene, germacrene [91]
Antitumour adenocarcinoma, = 0.86 µg mL-1; HCT-116: IC50 In vivo (in (Lamiaceae) D, myrcene,
Colon carcinoma, = 0.57 µg mL-1; SF-295: IC50 female Swiss trans-caryophyllene
Glioblastoma = 1.02 µg mL-1; mice)
In vivo: Sarcoma-180:
Intraperitoneal EO
(50–100 mg kg-1 day-1):
29.4–40.5% tumour growth
inhibition; Oral EO
(100–200 mg kg-1 day-1):
25.0–45.2% tumour growth
inhibition
Cytotoxicity Human breast cancer Location Chad: MCF-7: IC50 In vitro Monodora myristica α-phellandrene, limonene, [92]
= 0.295 µL mL-1; (Gaertn.) Dunal α-pinene, trans-thujen-3-ol, linalool
Location Cameroon: MCF-7: IC50 (Annonaceae)
= 0.265 µL mL-1
Cytotoxicity Breast cancer, EO (10–100 µL): MCF-7: In vitro Myristica fragrans β-pinene, α-pinene, α-thujene, p- [93]
Human melanoma inhibition = 3–64%; A375: Houtt. menth-1-en-4-ol
inhibition = 9–49% (Myristicaceae)
Anti- Human oral OEC-M1: IC50 = 38.9 µg mL-1; J5: In vitro Neolitsea trans-β-ocimene, sabinene, [94]
proliferative squamous carcinoma, IC50 = 42.6 µg mL-1; A549: IC50 variabillima α-cadinol, terpinen-4-ol,
Hepatocellular = 36.9 µg mL-1; HT-29: IC50 (Hayata) Kaneh. & τ-cadinol,
carcinoma, = 16.8 µg mL-1; UACC-62: IC50 Sasaki β-caryophyllene, α-pinene,
Lung = 8.8 µg mL-1; K562: IC50 (Lauraceae) β-pinene, 1,8-cineole,
adenocarcinoma, = 8.6 µg mL-1 γ-terpinene, bicyclogermacrene
Colon carcinoma,
Melanoma, Leukemia
Cytotoxicity Human ovarian (At 10–200 μg mL-1 for 24, 48, In vitro Nepeta ucranica L. Germacrene D, bicyclogermacrene, [95]
carcinoma, and 72 h): A2780: IC50 spp. kopetdaghensis β-bourbonene, β-elemene,
9
Plant family)
Human breast = 14.93 μg mL-1, MCF-7: IC50 (Pojark.) Rech.f. spathulenol, trans-caryophyllene,
adenocarcinoma = 25.21 μg mL-1 (Lamiaceae) palmitic acid
Anti- Prostate cancer, LNCaP: IC50 = 0.46 mg mL-1; PC- In vitro Ocimum basilicum L. α-terpineol, [21]
proliferative Human glioblastoma 3: IC50 = 0.45 mg mL-1; SF-763: (Lamiaceae) β-caryophyllene, α-humulene,
IC50 = 0.43 mg mL-1; SF-767: IC50 germacrene D, limonene, (E)-
= 0.30 mg mL-1 β-ocimene, myrcene, eucalyptol,
caryophyllene oxide, β-pinene
Cytotoxicity Human cervical HeLa: IC50 = 90.5 µg mL-1; HEp-2: In vitro Ocimum basilicum L. Methyl cinnamate, β-elemene, [96]
cancer, 96.5 µg mL-1 (Lamiaceae) camphor, linalool, mono (2-
Human laryngeal ethylhexyl) phthalate, anisole
epithelial carcinoma
Anti- Human cervix HeLa: IC50 = 86.11 µg mL-1; In vitro Ocimum basilicum L. Eugenol, isoeugenol, linalool [97]
proliferative adenocarcinoma, FemX: IC50 = 96.72 µg mL-1; (Lamiaceae)
Human melanoma, K562: IC50 = 159.78 µg mL-1;
Human chronic SKOV3: IC50 = >200 µg mL-1
myelogenous
leukemia,
Human ovarian
carcinoma
Anti- Human HepG2: EC50 = 0.18 µg mL-1; In vitro Ocimum basilicum L. Methyl chavicol, linalool, [72]
proliferative hepatocellular Caco2: EC50 = 0.071 µg mL-1; (Lamiaceae) α-bisabolene
carcinoma, MCF-7: EC50 = 0.17 µg mL-1;
Colon THP-1: EC50 = 0.67 µg mL-1
adenocarcinoma,
Breast
adenocarcinoma,
Leukemia
Anti- Human After 72 h EO treatment: HepG2: In vitro Origanum dictamnus Carvacrol, γ-terpinene, [98]
proliferative hepatocellular IC50 = 0.0069% (v/v) L. p-cymene, linalool, caryophyllene
carcinoma (Lamiaceae)
Anti- Melanoma, After 72 h EO: A375: IC50 In vitro Origanum onites L. Carvacrol, terp-1-in-4-ol, sabinene [99]
proliferative Breast cancer, = 8.90 µg mL-1; MCF-7: IC50 (Lamiaceae) hydrate, γ-terpinene,
Hepatocellular = 10.0 µg mL-1; HepG2: IC50 p-cymene, α-terpineol
carcinoma, = 23.0 µg mL-1; HT-29: IC50
Human colon cancer, = 0.35 µg mL-1; CT26: IC50
Mouse colon cancer = 1.10 µg mL-1
Antitumour Lewis carcinoma Decrease in tumour engraftment: In vivo (in F1 Origanum vulgare L. Carvacrol, β-fenchyl alcohol, thymol, [100],
tumour 52% (in control) to 29% (upon EO DBA C57 black (Lamiaceae) γ-terpinene[101] [101]
administration); decrease in hybrid mice)
tumour size by 1.5 times over the
control
Cytotoxicity; Hepatocellular In vitro: SMMC-7721: IC50 In vitro Oxytropis falcata Heneicosane, 6, 10, 14-trimethyl-2- [102]
Antitumour carcinoma, = 0.115 mg mL-1; In vivo (in male Bunge pentadecanone, 2-methylbenzyl
Murine hepatoma In vivo: H22: 19.5 and 27.2% at 30 ICR mice) (Leguminosae) cyanide, 4a, 8-tetramethyl-2-naph
and 60 mg kg-1 EO thalenem ethanol
Anti- Human HepG2: EC50 = 0.39 µg mL-1; In vitro Pimpinella anisum L. trans-anethole, pseudo-iso-eugenyl-2- [72]
proliferative hepatocellular Caco2: EC50 = 0.25 µg mL-1; (Apiaceae) methyl butyrate,
carcinoma, MCF-7: EC50 = 0.3 µg mL-1; THP- γ-himachalene
Colon 1: EC50 = 0.11 µg mL-1
adenocarcinoma,
Breast
adenocarcinoma,
Leukemia
Apoptosis Human oral YD-8: inhibition of proliferation In vitro Pinus densiflora 2,2-dimethyl-3- [103]
squamous cell by 30% and 60% upon treatment Siebold & Zucc. methylenenorbornane, α-pinene,
carcinoma with EO at 40 and 60 µg mL-1 for (Pinaceae) α-limonene, bornyl acetate
8 h; decrease in survival of cells
by ~60% at 20 or 40 µg mL-1 EO
and by 70% at 60 µg mL-1;
induction of apoptosis at
60 µg mL-1 EO for 8 h;
YD-10B: decrease in survival of
cells by 50% at 60 µg mL-1 EO for
8 h; YD-38: decrease in survival of
cells by 60% at 60 µg mL-1 EO for
8h
Cytotoxicity Acute lymphoblastic CCRF-CEM: IC50 = 43.84 µg mL-1; In vitro Pinus pinea L. Limonene, β-caryophyllene, [52]
leukemia CEM/ADR5000: IC50 (Pinaceae) α-terpineol,
= 61.54 µg mL-1 β-longipinene, α-caryophyllene
Anti- Human colon cancer, Inhibition of tumour proliferation In vitro Pinus roxburghii α-pinene, 3-carene, β-pinene, D- [104]
proliferative Human myelogenous (EO at 10–100 µg mL-1): HCT- Sarg. limonene, caryophyllene, longifolene,
leukemia, 116: 71%; KBM-5: 76%; U-266: (Pinaceae) caryophyllene oxide, humulene
Human multiple 83%; MiaPaCa-2: 73%; A-549: epoxide II
myeloma, 73%; SCC-4: 69%; increase in
10
Plant family)
Human pancreatic apoptotic cells (2.07–68.87% at

cancer, 25–100 µg mL-1)
Human lung
carcinoma,
Squamous cell
carcinoma
Antitumour Murine melanoma, In vitro: B16F10-Nex2: IC50 In vitro Piper cernuum Vell. Carvacrol, thymol, [105]
Human melanoma, = 39 µg mL-1; A2058: IC50 In vivo (in (Piperaceae) α-terpineol, linalol,
Human cervical = 24.6 µg mL-1; HeLa: IC50 C57B1/6 mice) α-pinene, camphene, limonene,
cancer, = 23.6 µg mL-1; HL-60: IC50 myrcene, p-cymene
Human myeloid = 15.5 µg mL-1; U87-MG: IC50
leukemia, = 19.0 µg mL-1;
Human glioblastoma In vivo: B16F10-Nex2: IC50
(camphene) = 71.2 µg mL-1
Anti- Human colon In vitro (after 48 and 72 h EO In vitro Pistacia lentiscus L. α-pinene, myrcene, β-pinene, [106]
proliferative carcinoma, treatment, respectively): HT-29: In vivo (in (Anacardiaceae) limonene, linalool
Murine colon IC50 = 0.1751 and 0.0762 mg mL- female BALB/c
1
carcinoma ; Caco-2: IC50 = 0.0368 and mice)
0.0176 mg mL-1; CT26: IC50
= 0.1335 and 0.0104 mg mL-1;
In vivo: inhibition of tumour
growth (52%) at EO = 0.58 g kg-1
body weight day-1
Cytotoxicity Liver cancer, HepG2: IC50 = 2.31 µg mL-1; In vitro Pituranthos tortuosus β-myrcene, sabinene, trans-iso- [107]
Colon cancer, HCT116: IC50 = 5.37 µg mL-1; (Desf.) Benth. & elemicin, terpinen-4-ol
Breast cancer MCF-7: IC50 = 9.93 µg mL-1 Hook. f. ex Asch. &
Schweinf.
(Apiaceae)
Anti- Melanoma In vitro: B16F10: In vitro Pituranthos tortuosus β-myrcene, sabinene, trans-iso- [107],
proliferative; increase in apoptotic cells In vivo (in (Desf.) Benth. & elemicin, terpinen-4-ol[107] [108]
Apoptosis; (40.5–74.5%) with increasing EO Balb/c male Hook.f. ex Asch. &
Antitumour concentrations (40–120 µg mL-1); mice) Schweinf.
In vivo: decrease in tumour weight (Apiaceae)
and size upon EO administration
at 50 and 100 mg kg-1 body
weight (98.33% and 98.26%
inhibition of tumour weight and
size, respectively)
Cytotoxicity Breast MCF-7: IC50 = 37.3 µM; A-549: In vitro Pluchea dioscoridis α-maaliene, berkheyaradulen, [69]
adenocarcinoma, IC50 = 22.3 µM (L.) DC. dehydro-cyclolongifolene oxide,
Lung cancer (Asteraceae) aromadendrene oxide-2,
β-muurolene, α-eudesmol,
β-caryophyllene, τ-muurolol
Cytotoxicity Human lung A549: IC50 = 12.05 µg mL-1; In vitro Populus alba L. 1,8-cineole, β-eudesmol, [109]
adenocarcinoma, H1299: IC50 = 10.53 µg mL-1; (Salicaceae) δ-cadinene
Human non-small cell MCF-7: IC50 = 28.16 µg mL-1
lung cancer,
Human breast
adenocarcinoma
Anti- Human SW1353: reduction in cell In vitro Pyrola japonica n-hexadecanoic acid, cedrol, 6,10,14- [110]
proliferative; chondrosarcoma viability with increasing EO Klenze ex Alef. trimethyl-2-pentadecanone, cis-9-
Cell cycle concentrations (50–150 µg mL-1) (Ericaceae) octadecadienoic acid
arrest for 48 h
Apoptosis and Non-small cell lung A549: IC50 = 36.43 µg mL-1 ; In vitro Rosa damascena β-citronellol, nonadecane, geraniol, [111]
necrosis carcinoma decrease in cell viability with Herrm. henicosane, eicosane, linalool, methyl
increasing EO concentrations (Rosaceae) eugenol
especially at higher doses
(50–200 µg mL-1)
Cytotoxicity Human lung A549: IC50 = 3.06 µg mL-1; In vitro Rosmarinus Camphor, verbenone, borneol, [109],
adenocarcinoma, H1299: IC50 = 4.34 µg mL-1; officinalis L. eucalyptol [112] [112]
Human non-small cell MCF-7: IC50 = 7.38 µg mL-1 (Lamiaceae)
lung cancer,
Human breast
adenocarcinoma
Cytotoxicity Human cervix HeLa: IC50 = 133.56 µg mL-1; In vitro Salvia lavandulifolia Camphor, 1,8-cineole, [82]
carcinoma, A549: IC50 = 140.10 µg mL-1 Vahl (Lamiaceae) α-pinene, camphene, β-pinene,
Lung (after 48 h EO treatment) limonene, linalool
adenocarcinoma
Anti- Human melanoma A375: IC50 = 10.7–46.3 µg mL-1; In vitro Salvia officinalis L. α-thujone, camphor, borneol, [113]
proliferative M14: IC50 = 8.2–48.6 µg mL-1; (Lamiaceae) γ-muurolene, sclareol
A2058: IC50 = 11.7–46.1 µg mL-1
Anti- Prostate carcinoma, LNCaP, MCF-7, HeLa: reduced cell In vitro Salvia officinalis L. 1,8-cineole, α-thujone, camphor [114]
proliferative Breast carcinoma, viability at 100 and 200 µg mL-1 (Lamiaceae)
Cervical carcinoma EO for 48 h; cytostatic effect at
11
Plant family)
100 µg mL-1 EO for 48 h in all the

cell lines;
At 200 µg mL-1 EO for 48 h:
LNCaP: cytostatic; MCF-7:
cytotoxic; HeLa: cytotoxic
Cytotoxicity Human colon After 24/48 h exposure of EO: In vitro Satureja Carvacrol, limonene [115]
adenocarcinoma, SW480: IC50 = 62.5 µg mL-1; khuzistanica Jamzad
Breast MCF-7: IC50 = 125 µg mL-1; JET3: (Lamiaceae)
adenocarcinoma, IC50 = 125 µg mL-1; Vero: IC50
Choriocarcinoma, = 31.2 µg mL-1
Kidney cancer
Cytotoxicity Human cervix HeLa: IC50 = 40.13 µg mL-1; In vitro Satureja montana L. Thymol, p-cymene, carvacrol, [82]
carcinoma, A549: IC50 = 65.51 µg mL-1 (after (Lamiaceae) γ-terpinene, β-bisabolene
Lung 48 h EO treatment)
adenocarcinoma
Cytotoxicity Human breast cancer, Region Galičica: MDA-MB-361: In vitro Satureja montana L. Carvacrol, thymol, carvacrol methyl [116]
Human epithelial IC50 = 234.6 ± 0.11 µg mL-1; subsp. pisidica ether, p-cymene, γ-terpinene,
cervical cancer, MDA-MB-453: IC50 (Wettst.) Šilić spathulenol, β-caryophyllene,
Human colon cancer = 240.3 ± 0.31 µg mL-1; HeLa: (Lamiaceae) β-linalool
IC50 = 99.7 ± 0.11 µg mL-1;
LS174: IC50
= 189.8 ± 0.31 µg mL-1;
Region Korab: MDA-MB-361: IC50
= 109.0 ± 0.21 µg mL-1; MDA-
MB-453: IC50
= 72.3 ± 0.11 µg mL-1; HeLa:
IC50 = 63.5 ± 0.31 µg mL-1;
LS174: IC50 = 99.4 ± 0.22 µg mL-
1
Anti- Mammary MCF-7: EC50 = 0.08% (v/v) after In vitro Satureja parnassica Carvacrol, thymol, p-cymene, [117]
proliferative adenocarcinoma 72 h EO treatment Heldr. & Sart. ex γ-terpinene
Boiss.
(Lamiaceae)
Anti- Mammary MCF-7: EC50 = 0.002% (v/v) after In vitro Satureja thymbra L. Carvacrol, thymol, p-cymene, [117]
proliferative adenocarcinoma 72 h EO treatment (Lamiaceae) γ-terpinene
Cytotoxicity Murine melanoma, B16F10-Nex2: IC50 = 38.0 µg mL- In vitro Schinus Germacrene D, bicyclogermacrene, [118]
1
Human melanoma, ; A2058: IC50 = 40.1 µg mL-1; terebinthifolius β-pinene,
Breast MCF-7: IC50 = 45.3 µg mL-1; HL- Raddi β-longipinene
adenocarcinoma, 60: IC50 = 20.0 µg mL-1; HeLa: (Anacardiaceae)
Leukemia, IC50 = 40.2 µg mL-1
Cervical carcinoma
Cytotoxicity Human glioblastoma, T98G: IC50 = 12.4 µg mL-1; MDA- In vitro Scorodopholeus 2,4,5,7-tetrathiaoctane, [36]
Human breast MB-231: IC50 = 8.0 µg mL-1; zenkeri Harms 2,3,5-trithiahexane,
adenocarcinoma, A375: IC50 = 17.7 µg mL-1; (Fabaceae) 2,4,5,6,8-pentathianonane,
Human malignant HCT116: IC50 = 8.5 µg mL-1 2,3,4,6-tetrathiaheptane
melanoma,
Human colon
carcinoma
Anti- Breast carcinoma, EO treatment at In vitro Semenovia (Z)-β-ocimene, linalool, [119]
proliferative; Colon carcinoma, 0.026–19.4 µL mL-1 for 48 h: suffruticosa (Freyn β-bisabolol
Apoptosis Neuroblastoma, MCF-7: IC50 = 5.0 µg mL-1; 60% & Bornm.) Manden.
Embryonal cells displayed early apoptosis (Apiaceae)
carcinoma when treated with EO at 5 µL mL-1
for 48 h; HT-29: IC50 = 1.5 µg mL-
1
; SH-SY5Y: IC50 = 4.2 µg mL-1;
NCCIT: IC50 = 0.72 µg mL-1
Cytotoxicity Oral cavity cancer, KB: IC50 = 26.42 µg mL-1; MCF-7: In vitro Solanum spirale (E)-phytol, [120]
Breast cancer, IC50 = 19.69 µg mL-1; NCI-H187: Roxb. n-hexadecanoic acid,
Small cell lung cancer IC50 = 24.02 µg mL-1 β-selinene,
α-selinene, octadecanoic acid,
hexahydrofarnesyl acetone
Cytotoxicity Breast tumour MCF-7: IC50 = 54.7 µg mL-1 In vitro Tagetes minuta L. (Z)-ocimenone, (E)-ocimenone, (Z)- [121]
(Asteraceae) β-ocimene, limonene, (Z)-tagetone,
dihydrotagetone,
dimethylvinylketone derivative
Cytotoxicity Liver carcinoma, Saudi Arabia region (at 100 ppm In vitro Thuja orientalis L. Egypt region: α-phellandrene, [122]
Breast carcinoma, EO): HepG2: 24.8%; MCF-7: (Cupressaceae) β-caryophyllene, terpenyl acetate,
Colon carcinoma, 47.6%; HCT-116: 32.0%; PC-3: α-cedrol;
Prostate carcinoma, 10.4%; A549: 11.2%; Saudi Arabia region: limonene,
Lung carcinoma Egypt region (at 100 ppm EO): α-phellandrene,
HepG2: 21.3%; MCF-7: 35.4%; β-caryophyllene, α-cedrol
HCT-116: 29.5%; PC-3: 8.4%;
A549: 13.2%
Cytotoxicity KB: IC50 = 0.44 µL mL-1 In vitro [123]
12
Plant family)
Human oral Thymus carmanicus Carvacrol, cymene, thymol, borneol,

epidermoid Jalas γ-terpinene,
carcinoma (Lamiaceae) β-myrcene
Antioxidant Colorectal cancer DLD-1: IC50 = 0.347 mg mL-1 In vitro Thymus fallax Fisch. Carvacrol, p-cymene, thymol, [124]
& C.A.Mey. γ-terpinene
(Lamiaceae)
Cytotoxicity; Lung metastasis In vitro: B16F-10: 70.23% cancer In vitro Tridax procumbens α-pinene, 1,3,6-octatriene, [125]
Apoptosis cells died at 50 µg EO for 24 h; In vivo (in L. β-pinene, camphene, phellandrene,
71.67% inhibition in tumour C57BL/6 male (Asteraceae) sabinene,
formation upon EO mice) β-ocimene, L-limonene, trans-
administration; increase in β-ocimene, trans-caryophyllene,
apoptotic cells γ-elemene, torreyol, spathulenol,
aromadendrene
Cytotoxicity Human breast cancer, MDA-MB-231: IC50 = 0.3 µg mL-1; In vitro Varthemia Eucalyptol, bornyl acetate, borneol [126]
Chronic myelogenous K-562: IC50 = 0.4 µg mL-1; Panc1: iphionoides Boiss. &
leukemia, IC50 = 0.4 µg mL-1; PC-3: IC50 Blanche
Pancreatic cancer, = 0.14 µg mL-1; PDL: IC50 (Asteraceae)
Prostate cancer, = 0.3 µg mL-1
Human periodontal
ligament fibroblasts
Anti- Mouse melanoma In vitro: death of cancer cells In vitro Wedelia chinensis Carvacrol, trans-caryophyllene, [27]
proliferative (65.17%) upon 50 µg EO In vivo (in (Osbeck) Merr. β-myrcene, α-terpinene,
administration for 24 h; increase C57BL/6 male (Asteraceae) γ-terpinene,
in apoptotic cells;; mice) ortho-lymene, α-bergamotene,
In vivo: inhibition of tumour α-humulene,
growth upon EO administration at aromadendrene, 3-decynex, thymol
50 µg mL-1 animal-1
Cytotoxicity Human breast cancer Location Chad: MCF-7: IC50 In vitro Xylopia aethiopica β-pinene, sabinene, [92]
= 0.325 µL mL-1; (Dunal) A.Rich β-phellandrene, γ-terpinene, terpinen-
Location Cameroon: MCF-7: IC50 (Annonaceae) 4-ol
= ~0.600 µL mL-1
Cytotoxicity Ovarian In vitro: OVCAR-8: IC50 In vitro Xylopia frutescens (E)-caryophyllene, [127]
adenocarcinoma, = 33.9 µg mL-1; NCI-H358M: IC50 In vivo (in Aubl. bicyclogermacrene, germacrene D,
Bronchoalveolar lung = 24.6 µg mL-1; PC-3 M: IC50 Swiss mice) (Annonaceae) δ-cadinene, viridiflorene,
carcinoma, = 40.0 µg mL-1 α-copaene
Metastatic prostate In vivo: Sarcoma 180: inhibition of
carcinoma tumour growth by 31.0–37.5% at
50 and 100 mg kg-1 day-1 EO
Cytotoxicity; Promyelocytic In vitro: In vitro Xylopia laevigata γ-muurolene, δ-cadinene, germacrene [128]
Antitumour leukemia, Sample A: HL-60: IC50 In vivo (in male (Mart.) R.E. Fr. B, α-copaene, germacrene D,
Ovarian carcinoma, = 17.5 µg mL-1; OVCAR-8: IC50 Swiss mice) (Annonaceae) bicyclogermacrene,
Glioblastoma, = 31.6 µg mL-1; SF-295: IC50 (E)-caryophyllene
Colon carcinoma = 14.4 µg mL-1; HCT-116: IC50
= 22.2 µg mL-1;
Sample B: HL-60: IC50
= 25.0 µg mL-1; OVCAR-8: IC50
= 27.1 µg mL-1; SF-295: IC50
= 17.9 µg mL-1; HCT-116: IC50
= 25.5 µg mL-1;
Sample C: HL-60: IC50
= 20.6 µg mL-1; OVCAR-8: IC50
= 18.5 µg mL-1; SF-295: IC50
= 20.5 µg mL-1; HCT-116: IC50
= 27.6 µg mL-1;
In vivo: Sarcoma 180: decrease in
tumour weight and growth
inhibition rate = 37.3–42.5% at
50 and 100 mg kg-1 day-1 EO,
respectively
Cytotoxicity Human breast cancer Location Chad: MCF-7: IC50 In vitro Xylopia parviflora Sabinene, [92]
= 0.155 µL mL-1; Spruce β-phellandrene, δ-cadinene,
Location Cameroon: MCF-7: IC50 (Annonaceae) α-muurolene, γ-muurolene, trans-
= 0.166 µL mL-1 muurola-4(14),5-diene, epi-α-cadinol,
α-muurolol,
α-pinene, β-pinene, trans-pinocarveol,
myrtenol
Anti- Prostate cancer, LNCaP: IC50 = 0.38 mg mL-1; PC- In vitro Zingiber officinale Arcurcumene, β-bisabolene, [21]
proliferative Human glioblastoma 3: IC50 = 0.42 mg mL-1; SF-763: Roscoe zingiberene, camphene,
IC50 = 0.44 mg mL-1; SF-767: IC50 (Zingiberaceae) β-sesquiphellandrène, eucalyptol,
= 0.48 mg mL-1 α-pinene,
β-phellandrene, limonene, borneol,
geranial
Cytotoxicity; Dalton’s lymphoma In vitro: DLA: IC50 = 11.0 µg mL-1; In vitro Zingiberene, citronellyl n-butyrate, [129],
Antitumour ascites, EAC: IC50 = 18.0 µg mL-1; In vivo valencene, [130]
13
Plant family)
Ehrlich ascites In vivo: decrease in tumour (in male Swiss Zingiber officinale β-phellandrene, β-funebrene,
carcinoma volume (3.75 cm3 in control) to albino mice) Roscoe selina-4(14), 7(11)-diene, camphene,
1.97–1.41 cm3 at (Zingiberaceae) α-pinene[130]
100–1000 mg kg-1 body weight
EO; increase in mice survival from
18.75% to 50% at
100–1000 mg kg-1 body weight
EO
Cytotoxicity Human leukemia, Flower oil: K562: IC50 In vitro Zingiber striolatum Flower oil: β-phellandrene, [131]
Human prostatic = 26.75 µg mL-1; PC-3: IC50 Diels α-humulene, β-pinene, β-elemene,
carcinoma, = 82.56 µg mL-1; A549: IC50 (Zingiberaceae) humulene oxide II, cryptone,
Human lung cancer = 52.65 µg mL-1; tricosane;
Leaf oil: K562: IC50 Leaf oil: hexahydrofarnesyl acetone,
= 37.89 µg mL-1; PC-3: IC50 α-humulene, phytol, humulene oxide
= 77.20 µg mL-1; A549: IC50 II, β-pinene, sandaracopimaradiene,
= 45.73 µg mL-1; β-elemene;
Stem oil: K562: IC50 Stem oil: α-humulene, humulene
= 12.94 µg mL-1; PC-3: IC50 oxide II, hexahydrofarnesyl acetone,
= 69.06 µg mL-1; A549: IC50 phytol, humulene oxide I, β-elemene,
= 66.12 µg mL-1 4-terpineol
Cytotoxicity; Mouse melanoma, In vitro: B16-F10: IC50 In vitro Zornia brasiliensis trans-nerolidol, germacrene D, trans- [132]
Antitumour Human = 4.93 µg mL-1; HepG2: IC50 In vivo (in Vogel caryophyllene,
hepatocellular = 1.05 µg mL-1; HL-60: IC50 C57BL/6 male (Leguminosae) α-humulene, (Z,E)- α-farnesene
carcinoma, = 9.58 µg mL-1; K562: IC50 mice)
Human = 7.26 µg mL-1;
promyelocytic In vivo: inhibition of tumour
leukemia, growth (1.68–38.61%) at 50 and
Human chronic 100 mg kg-1 day-1 EO
myelocytic leukemia
including disruption of cell membrane (depolarization, increase in cancer (LNCaP, PC-3) cell lines largely due to the predominance of
membrane permeability, or reduction in the activity of membrane- precocene, caryophyllene, β-sesquiphellandrene, and germacrene D
bound enzymes), and induction of apoptosis [32] (Fig. 3). Indeed, Lit [21]. EO of Allium sativum L. (garlic) and/or its organosulphur compo
sea cubeba (Lour.) Pers. seed oil decreased the proliferation of non-small nents also exhibit anticancer activity due to induction of apoptosis and
cell lung carcinoma cells and induced caspase-mediated apoptosis and increase in ROS generation [37]. EO of the peels of Citrus aurantium L.
G1/S phase cell cycle arrest [33]. It was evident from up-regulation of subsp. amara (Link.) Engl., characterized by the presence of limonene
mTOR (mechanistic target of rapamycin) and p21 proteins and and myrcene, was cytotoxic against colorectal cancer cells (Lim1863),
down-regulation of PPDK1 (protein pyruvate dehydrogenase kinase 1) which correlated with a significant reduction (>80%) in viability at
phosphorylation, PKB (protein kinase B), and mdm2 (murine double lower concentrations [53]. Likewise, the EOs of Eucalyptus sp. (E.
minute 2) [33]. Likewise, increase in apoptosis of cervical cancer cells camaldulensis .and E. globulus Labill.) demonstrated cytotoxicity against
through activation of caspases, cleavage of substrates such as poly-ADP colorectal cancer and lung cancer, respectively, and the IC50 value was
ribose polymerase (PARP), release of mitochondrial cytochrome c, and 100 µg mL-1 in Caco-2 colorectal cancer cells [25,70]. EO of the leaf/
phosphorylation of Akt (a serine-threonine specific protein kinase) and flower/fruits of Liriodendron tulipifera L. exhibited cytotoxicity against
mTOR protein has been described by the action of carvacrol (an EO human hepatocellular carcinoma (HepG2), human ductal carcinoma
constituent) [34]. (Hs578T), and human breast adenocarcinoma, owing to the presence of
β-elemene, germacrene D, and (E)-nerolidol [87]. The anti-proliferative
3.2. Functional crosstalk between EOs/their constituents and cancer cell activity of Mentha spicata L. against hepatocellular carcinoma (HepG2),
lines: A collection of previous investigations colon adenocarcinoma (Caco-2), breast adenocarcinoma (MCF-7), and
leukemia (THP-1) has been illustrated by the authors with EC50 values of
Over the past few years, cancer chemoprevention using EOs or their 0.22 µg mL-1, 0.162 µg mL-1, 0.284 µg mL-1, and 0.71 µg mL-1, respec
components has garnered a great deal of research attention. Many in tively [73]. EO of Neolitsea variabillima (Hayata) Kaneh. & Sasaki
vitro/in vivo studies have highlighted the anticancer activity of EOs/their inhibited the proliferation of various cancer cell lines (OEC-M1, A549,
major constituents in different tumour cell lines (Tables 1 and 2). A brief HT-29, UACC-62, and K562) owing to the presence of trans-β-ocimene,
description of some EOs and their constituents in providing protection sabinene, α-cadinol, terpinen-4-ol, τ-cadinol, β-caryophyllene, α-pinene,
against various cancers is given below. β-pinene, 1,8-cineole, γ-terpinene, and bicyclogermacrene [94]. EO of
Satureja montana L. dominated by thymol, p-cymene, carvacrol, γ-ter
3.2.1. Anticancer effect of EOs pinene, and β-bisabolene in its EO fraction, inhibited the growth of
EOs of Abies alba Mill. and Abies koreana E.H. Wilson exhibited human cervix carcinoma and lung adenocarcinoma cell lines with IC50
cytotoxicity in breast cancer cell lines (MCF-7 and MDA-MB-231) with values of 40.13 µg mL-1 and 65.51 µg mL-1, respectively [82].
an IC50 value of 100.0 µg mL-1 [35]. The presence of α-pinene, β-pinene,
limonene, β-myrcene, camphene, and bornyl acetate contributed to the 3.2.2. Anticancer effect of major EO constituents
cytotoxic behaviour of the oils [35]. EO of Afrostyrax lepidophyllus D-Limonene, a monoterpene in the fruit peels of citrus EOs (90–95%)
Mildbr. was cytotoxic to various cancer cell lines such as T98G (glio exhibited cytotoxicity against gastric cancer [7], hepatocellular carci
blastoma), MDA-MB-231 (breast adenocarcinoma), A375 (melanoma), noma [55], colon cancer [55,174], bladder cancer [175], and melanoma
and HCT116 (colon carcinoma) [36]. EO of Ageratum conyzoides (L.) L. [55]. Likewise, carvacrol (a phenolic monoterpenoid) can suppress the
inhibited the growth of glioblastoma (SF-763, SF-767) and prostate growth of tumour in gastric cancer cells through increase in apoptotic
14
Table 2
In vitro/in vivo cytotoxicity and anti-proliferative activity of some major essential oil constituents in different tumour cell lines.
Essential oil Type of cancer (s) Targeted cancer cell lines and IC50/EC50 In vitro/ Major observation (s) References
constituent (s) prevented values In vivo studies
Bakuchiol Human gastric (At 0–120 µg mL-1 bakuchiol for 24 h): NUGC3: In vitro 1. Inhibition of cell viability; [133]
carcinoma IC50 = 120.0 μg mL-1 2. Induction of apoptosis, cell death,
and cell cycle arrest (% of cells in sub-
G1 phase: 28% and 39% at 50 and
100 µg mL-1 bakuchiol);
3. Cleavage of caspase-3 and PARP,
higher Bax/Bcl-xl ratio, decreased AKT
phosphorylation, and increased levels
of ERK1/2, JNK, and p38 favoured
apoptosis
α-Bisabolol Pancreatic cancer KLM1, KP4, Panc1 In vitro 1. Suppression of invasion and cell [134]
migration upon treatment with
1.56 µM α-bisabolol for 24 h;
2. Up-regulation of metastasis-
suppressor gene such as KISS1R and
TIMP2
α-Bisabolol Endometrial cancer (At 0–32 µmol L-1 α-bisabolol for 24 h): In vitro 1. Growth inhibition of all the cancer [135]
RL95–2: EC50 = 8.4 µmol L-1, LC50 cell lines;
= 3.6 µmol L-1, ECC001: EC50 = 7.6 µmol L-1, 2. Decrease in cancer cell migration [%
LC50 = 3.5 µmol L-1, ECC003: EC50 wound left = 68.5% (for RL95–2) and
= 6.5 µmol L-1, LC50 = 3.1 µmol L-1, Ishikawa: 42.0% (ECC001) after 24 h treatment
EC50 = 9.1 µmol L-1, LC50 = 3.6 µmol L-1 with 4 µmol L-1 α-bisabolol];
3. Reduction in cell invasion by 57.5%
(in RL95–2) and 27% (in ECC001);
4. Induction of apoptosis
Bornyl acetate Human gastric (At 0–96 µM bornyl acetate): SGC-7901 In vitro 1. Increased inhibitory effect was [136]
cancer observed with the combination
formulation;
2. Decline in number of colonies of
cancer cells;
3. Increase in apoptosis (observable
features: chromatin condensation,
nuclear fragmentation and shrinkage)
and % of apoptotic cells = 15.4% (for
48 µM bornyl acetate);
4. Arrest of cells in G2/M phase of cell
cycle
Camphene; Human melanoma, In vitro (At 0–100 µg mL-1 camphene for 24 h): In vitro 1. Cytotoxic effect of camphene was [105]
α-Pinene; Breast cancer, A2058: IC50 = 35.2 ± 1.2 μg mL-1, SKBR-3: In vivo (in observed in all the cancer cell lines;
Limonene; Carvacrol; Cervical cancer, IC50 = 34.7 ± 2.5 μg mL-1, HeLa: IC50 C57Bl/6 mice) 2. Induction of apoptosis (observable
Thymol; Myrcene; Human myeloid = 110.1 ± 5.1 μg mL-1, HL-60: IC50 parameters: shrunken cells,
p-Cymene; leukemia, = 27.0 ± 2.0 μg mL-1, U87-MG: IC50 condensation and fragmentation of
α-Terpineol; Human = 55.4 ± 1.6 μg mL-1, B16F10-Nex2: IC50 DNA);
Linalool glioblastoma, = 71.2 ± 4.3 μg mL-1 (for camphene), IC50 3. B16F10-Nex2: Endoplasmic
Murine melanoma = 24 ± 0.4 μg mL-1 (for α-pinene); IC50 reticulum condensation
= 59 ± 3.0 μg mL-1 (for limonene); IC50 (at 70 µg mL-1 camphene) and loss of
= 82 ± 4.0 μg mL-1 (for carvacrol); IC50 mitochondrial membrane potential;
= 88 ± 0.7 μg mL-1 (for thymol); IC50 4. Increased expression of caspase-3,
= >100 μg mL-1 (for myrcene, p-cymene, calreticulin, and HmgB1 upon
α-terpineol, treatment with 70 µg mL-1 camphene;
linalool); 5. In vivo: Decrease in tumour volume
In vivo: 10 µg mL-1 camphene for 10–20 days especially from 16th to 20th day after
treatment with 10 µg mL-1 camphene
daily
Carvacrol Human Caucasian (At 10–600 µmol L-1 carvacrol for 24 h): AGS: In vitro 1. Decrease in cell viability (94.11% [137]
gastric IC50 = 82.57 ± 5.58 µmol L-1 and 0.54% at 10 and 600 µmol L-1
adenocarcinoma carvacrol, respectively);
2. Increased ROS production upon
treatment with 20–600 µmol L-1
carvacrol for 24 h;
3. Decrease in GSH content with
increasing concentrations of carvacrol;
4. Increase in apoptosis and necrosis at
10–100 µmol L-1 carvacrol for 24 h
(visible characters: shrunken nuclei,
condensed chromatin);
5. Increase in apoptotic proteins (Bax)
and caspases (3 and 9), whereas
decrease in anti-apoptotic proteins
(Bcl-2)
Carvacrol Human U87: IC50 = 322 µM, MDA-MB-231: IC50 In vitro Decrease in cancer cell viability [138]
glioblastoma, = 199 µM
15
Mammary gland
adenocarcinoma
Carvacrol Human cervical (At 25–500 mg L-1 for 48 h): HeLa: IC50 In vitro 1. Cytotoxic effect of carvacrol was [139]
cancer = 50 ± 5.95 mg L-1, SiHa: IC50 observed in the tested cell lines after
= 50 ± 3.89 mg L-1 48 h;
Carvacrol Human (At 0.05–0.4 mmol L-1 for 24 h): HepG-2: IC50 In vitro 1. Decrease in cell viability with [140]
hepatocellular = 0.4 mmol L-1 increasing concentrations of carvacrol;
carcinoma 2. Increase in apoptosis (features:
chromatin fragmentation) and
apoptosis rate (= 13.5–50.6% at
0.05–0.4 mmol L-1) due to decreased
Bcl-2 levels, increased expression of
caspases and PARP cleavage, increased
expression of MAPK and p38,
decreased ERK1/2 phosphorylation
Carvacrol Human cervical (At 550 µM carvacrol): HeLa: IC50 In vitro 1. Increased cytotoxicity; [34]
cancer = 556 ± 39 µM 2. Induction of apoptosis as a result of
cleavage of caspase-9 and PARP;
3. Decline in phospho-Akt, mTOR, and
phosphor-mTOR protein levels as a
result of autophagy
Carvacrol; Murine Carvacrol: P-815: IC50 = 0.067 µM, K-562: IC50 In vitro 1. Cytotoxic effect was observed in the [141]
Thymol; mastocytoma, = 0.067 µM, CEM: IC50 = 0.042 µM, MCF-7: tested cancer cell lines (especially P-
Carveol; Human chronic IC50 = 0.125 µM, MCF-7 gem: IC50 = 0.067 µM; 815 and CEM); carvacrol was the most
Carvone; myelogenous Thymol: P-815: IC50 = 0.15 µM, K-562: IC50 toxic;
Eugenol; leukemia, = 0.44 µM, CEM: IC50 = 0.31 µM, MCF-7: IC50 2. Cytotoxicity was synergistically
Isopulegol Acute T = 0.48 µM; increased upon combination treatment
lymphoblastoid Carveol: P-815: IC50 = 0.11 µM, K-562: IC50 with methotrexate and cis-platin
leukemia, = 0.13 µM, CEM: IC50 = 0.11 µM, MCF-7: IC50 anticancer drugs;
Human breast = 0.26 µM, MCF-7 gem: IC50 = 0.45 µM; 3. Cell cycle arrest in S phase (in
adenocarcinoma Carvone: P-815: IC50 = 0.16 µM, K-562: IC50 carvacrol and carveol) and G0/G1 (in
= 0.17 µM, CEM: IC50 = 0.11 µM, MCF-7: IC50 thymol and isopulegol)
= 0.63 µM, MCF-7 gem: IC50 = 0.91 µM;
Eugenol: P-815: IC50 = 0.10 µM, K-562: IC50
= 0.24 µM, CEM: IC50 = 0.09 µM, MCF-7: IC50
= 0.41 µM, MCF-7 gem: IC50 = 0.87 µM;
Isopulegol: P-815: IC50 = 0.09 µM, K-562: IC50
= 0.13 µM, CEM: IC50 = 0.11 µM, MCF-7 gem:
IC50 = 0.25 µM
Carvacrol; Hepatoma HepG2: 10–3000 µg mL-1 for 24 h; In vitro 1. Decrease in cell viability with [142]
Thymol Carvacrol: HepG2: IC50 = 53.09 µg mL-1; increase in concentrations
Thymol: HepG2: IC50 = 60.01 µg mL-1 (20–170 µg mL-1);
2. Anti-proliferative activity,
cytotoxicity, and induction of
membrane damage were largely
responsible for the anticancer effect
β-Caryophyllene oxide Breast cancer, (At 30 or 50 µM): MCF-7, PC-3 In vitro 1. Reduced proliferation of cancer [143]
Prostate cancer cells, cell cycle arrest in sub-G1 phase,
and induction of apoptosis;
2. Down-regulation of anti-apoptotic
proteins (mTOR, S6K1, AKT/ PI3K)
activation of MAPK cascade (by
increasing the levels of p38, JNK, and
ERK);
3. Decrease in cyclin D1 while increase
in caspases and PARP cleavage;
4. Increased expression of p53 and p21
in PC-3 cancer cells
Citral Breast cancer MDA-MB-231 spheroid cells at 2.5, 5.0, and In vitro 1. Reduction in volume and size of [144]
10.0 µg mL-1 for 48 h: IC50 spheroids;
= 10.00 ± 0.14 μg mL-1 2. Decline in number of primary
spheroids from 20 in control to 6 with
10.0 µg mL-1 citral
3. Reduction in number of secondary
spheroids formation;
4. Anti-proliferative and apoptotic
activities contributed to cancer
prevention
Citral Endometrial cancer Ishikawa and ECC-1: IC50 = 15–25 µM (or In vitro Anti-proliferative activity [145]
2.28–3.8 μg mL-1)
Citral Prostate cancer, LNCaP: IC50 = 4.3 μg mL-1; PC-3: IC50 In vitro Anti-proliferative activity [65]
Glioblastoma = 14.3 μg mL-1; SF-767: IC50 = 22.4 μg mL-1;
SF-763: IC50 = 35.3 μg mL-1
Citral In vitro [146]
16
Small cell lung LU134AM: IC50 = 68.31 ± 1.43 μM, LU135: 1. Anti-proliferative activity of citral
carcinoma IC50 = 62.24 ± 2.73 μM, LU165: IC50 with increasing concentrations in all
= 83.07 ± 0.61 μM, MN1112: IC50 cell lines;
= 82.31 ± 5.71 μM 2. Increase in apoptosis upon
treatment with citral at 150 and
400 μM;
3. Increase in anti-proliferative
activity through combination
treatment of citral and
chemotherapeutic agents (on LU165
and MN1112 cells)
Citral Colorectal (At 3.12–200 μM citral for 24–72 h): HCT116: In vitro 1. Citral was cytotoxic to cancer cell [147]
carcinoma IC50 = 145.32 μM, 85.47 μM, and 52.63 μM, lines tested;
respectively at 24, 48, and 72 h; 2. Cell death and apoptosis was
HT29: IC50 = 181.21 μM, 143.61 μM, and induced by citral, increase in apoptotic
91.5 μM at 24, 48, and 72 h, respectively cells (HCT116: 38.4–69.6% and HT29:
21.6–53.8% with 50–200 μM citral for
48 h)
Citral Stomach cancer (At 7.5–200 μg mL-1 citral for 48 h): AGS cell In vitro 1. Reduction in cell proliferation, [148]
lines induction of cell death (at
5–100 μg mL-1 citral), inhibition of
invasion and migration of cancer cells
(at 0–40 μg mL-1 citral);
2. Increasing concentrations of citral
(5, 10, and 20 μg mL-1) increased the
number of apoptotic cells, induced
DNA fragmentation, chromatin
condensation, and produced shrunken
nuclei
Citral Acute promyelocytic (At 0–20 μg mL-1 citral for 12, 24, and 48 h): In vitro 1. Increased cytotoxicity with [149]
leukemia NB4: IC50 = 3.995 μg mL-1 increasing citral concentrations;
2. Increased apoptotic activity (at
5–20 μg mL-1 citral for 24 h) from
55.67 ± 2.13% to 97.33 ± 2.89%
Citral Murine melanoma, Citral (at 0.1–2.5 μM for 24 h): B16F10: IC50 In vitro 1. Decreased B16F10 cell proliferation [150]
Human melanoma = 1.04 μM, SK-MEL-147: IC50 = 11.7 μM, (at ≥0.5 μM for 24 h and ≥0.05 μM for
UACC-257: IC50 = 13.4 μM, HaCaT: IC50 48 h) and reduced cell viability (at
= 50.3 μM, NIH-3T3: IC50 = 2.50 μM ≥0.5 μM for 24 and 48 h);
2. Increase in apoptotic (at 1.0 μM)
and necrotic (at 2.5 μM) cells;
3. Induction of autophagy (at 1.0 μM
citral) in B16F10 cancer cells;
4. Induction of apoptosis (in SK-MEL-
147, NIH-3T3, and UACC-257) with
≥ 5.0 μM citral and (in HaCaT) with
≥ 25.0 μM citral;
5. Necrosis: SK-MEL-147 and UACC-
257: ≥ 20.0 μM, HaCaT: ≥ 50.0 μM,
NIH-3T3: ≥ 5.0 μM
Citral Human squamous (At 0–400 μg mL-1 citral): A431 In vitro Decrease in cell viability with [151]
carcinoma increasing concentrations of citral (=
95% and 4% at 50 and 400 μg mL-1,
respectively)
Citral Colorectal cancer (At 1.56–25 μg mL-1 citral for 24, 48, and 72 h): In vitro Anti-proliferative and cytotoxic effect [152]
HT29: IC50 = 21.77 ± 0.23 μg mL-1 (at 72 h), of citral was responsible for its
SW620: IC50 = 22.50 ± 2.50 μg mL-1 (at 72 h) anticancer activity
Citral Human Burkitt’s Cytotoxicity (At 0–160 μM citral for 24 h) in In vitro 1. Increased cytotoxicity; [153]
lymphoma Ramos cells: IC50 = 77.19 ± 4.95 μM; 2. Induction of apoptosis and cell
Apoptosis (At 10, 20, and 40 μM citral for 18 h) death with 40 μM citral;
in Ramos cells; 3. Increase in pro-apoptotic proteins
Anti-proliferation study (At 10, 20, and 40 μM such as BAK upon treatment with
citral for 3 h) in Ramos cells 40 μM citral;
4. Increase in anti-proliferative
activity when treated with 40 μM
citral
Citral; Breast cancer Cytotoxicity (At 10–320 μg mL-1): MCF-7: IC50 In vitro 1. Anti-proliferative activity of citral [154]
Geraniol = 174.5 μg mL-1 for citral and 138.9 μg mL-1 and geraniol was observed (IC50 =
for geraniol 140.7 μg mL-1 for citral and
117 μg mL-1 for geraniol);
2. Citral and geraniol also exhibited
cytotoxic effects in cancer cells
Citral; Breast cancer MCF-7 and MDA-MB-231 for 24, 48, and 72 h; In vitro 1. MCF-7: EC50 and EC75 [155]
Curcumin; MCF-7: Curcumin (at 0–80 µM): IC50 = 40 μM; concentrations for combination of
Combination of citral Citral (at 0–160 µM): IC50 = 80 μM; citral and curcumin acted
and curcumin synergistically for anticancer activity;
17
MDA=MB-231: Curcumin (at 0–80 µM): IC50 2. MDA-MB-231: EC75 concentration

= 50 μM; Citral (at 0–160 µM): IC50 = 100 μM acted synergistically;
3. MCF-7: Increase in apoptotic cells
treated with 40 μM curcumin and
80 μM citral, and combined treatment
of curcumin and citral at EC50
concentration;
4. Decrease in cell viability (Curcumin:
67.0–30.2%, Citral: 63.5–30.2%);
5. Increased DNA damage, cell cycle
arrest in G0/G1 phase with curcumin
and combined treatment of curcumin
and citral at 24 and 48 h
Citronellol Human non small- In vitro (24 and 48 h, respectively): A549: IC50 In vitro 1. Cytotoxic effect of citronellol was [156]
cell lung carcinoma, = 69.10 and 54.02 μg mL-1, NCI-H23: IC50 In vivo (in 7- observed in all the cancer cell lines,
Breast cancer, = 63.53 and 52.51 μg mL-1, NCI-H1299: IC50 week-old BALB/ NCI-H1299 being more potent;
Prostate cancer = 49.74 and 40.64 μg mL-1, BT-20: IC50 c nude mice) 2. Cell cycle arrest in G1 phase in NCI-
= 61.23 and 45.84 μg mL-1, PC3: IC50 = 60.83 H1299 cells;
and 50.10 μg mL-1; 3. Decreased expression of cyclins (E
In vivo: 12.5, 25, and 50 mg kg-1 citronellol 5 and D) and CDK2, thus, G1 to S phase
days/week for 4 weeks transition was inhibited;
4. Cell death, necrosis, and increased
ROS accumulation;
5. Decrease in mice tumour volume
with increasing citronellol
concentrations
Citronellol; Breast cancer MDA-MB-231 (Citronellol: IC50 = In vitro 1. Decreased cell viability; [157]
Citronellal 1.16 ± 0.10 nM, Citronellal: IC50 = 2. Anti-proliferative activity was
1.41 ± 0.03 nM) observed at 0.5–1 nM citronellol and
citronellal from 24 to 48 h;
3. Decreased cell migration (from 6 to
24 h with 0.5–1 nM citronellol and
citronellal);
4. Cells were arrested in G2/M phase
of cell cycle;
5. Increase in apoptotic cells
[Citronellol (1 nM): 14.30 ± 0.89%,
Citronellal (1 nM): 13.92 ± 0.31%]
Diallyl disulfide (DADS) Esophageal (At 10–60 μg mL-1): ECA109: IC50 In vitro 1. Decrease in cell viability; [158]
squamous cell = 49.02 ± 4.78 μg mL-1 at 24 h, 2. Arrest of cancer cells in G2/M phase
carcinoma 33.14 ± 5.02 μg mL-1 at 48 h, and of cell cycle especially upon treatment
22.74 ± 4.05 μg mL-1 at 72 h with 20–60 μg mL-1 (increase in cells
= 58.65 ± 3.79%);
3. Induction of apoptosis (rate =
14.48 ± 0.99% at 20 μg mL-1,
42.68 ± 2.08% at 40 μg mL-1, and
72.96 ± 3.43% at 60 μg mL-1) through
increase in Bax while a decrease in Bcl-
2 protein, p-MEK1, and p-ERK1/2;
4. Decrease in the expression of cell
cycle progression proteins (cyclin B1,
cdc25c, and p-cdc2) and increase in
p21 protein and caspase-3
β-Elemene Murine melanoma (At 0–1000 µM for 48 and 120 h): B16F10: IC50 In vitro 1. Anti-proliferative effect of [159]
= 468.8 µM; In vivo (C57/BL6 β-elemene was observed at doses
In vivo: At 20 and 50 mg kg-1 β-elemene male mice and higher than 200 µM;
6-weeks-old 2. Decrease in expression of VEGF
Sprague-Dawley especially at 50 µM after 4 h in vitro;
rats) 3. Decrease in tumour size after 21
days treatment, reduction in formation
of lung metastatic colonies after 42
days;
4. Inhibition of VEGF in vivo (decrease
from 357.1 ± 79.5 ng L-1 to
139.2 ± 38.1 ng L-1 and
96.8 ± 18.7 ng L-1 at 20 and 50 mg kg-
1
β-elemene, respectively)
β-Elemene Human non-small- A549: IC50 = 53.5 µg mL-1 and 36.5 µg mL-1 at In vitro 1. Decrease in cell viability; [160]
cell lung cancer 24 and 48 h, respectively 2. Induction of apoptosis due to PARP
cleavage, decreased Bcl-2 and survivin
proteins at 50 µg mL-1 for 24 h;
3. At 40 µg mL-1 for 24 h: decreased
phosphorylation of Akt, mTOR, and
p70S6K1;
4. Induction of autophagy at 10 µg mL-
18
1
(LC3-positive puncta = 20%) and
50 µg mL-1 (LC3-positive puncta =
80%) and increase in levels of LC3-II
and Atg5-Atg12
β-Elemene Human hepatoma (At 0–120 µg mL-1 for 0–96 h): HepG2 In vitro 1. Proliferation of cancer cells was [161]
inhibited (= 73.7 ± 4.4% at 40 µg mL-
1
for 96 h);
2. Induction of apoptosis (% of
apoptotic cells = 19.28 ± 4.72 at
10 µg mL-1, 38.65 ± 5.52% at
20 µg mL-1, and 67.54 ± 7.35% at
40 µg mL-1 and apoptosis rate =
18.92 ± 5.16% at 10 µg mL-1,
32.83 ± 6.25% at 20 µg mL-1, and
51.33 ± 8.46% at 40 µg mL-1);
3. Cancer cells in sub-G1 phase
(apoptosis ratio = 5.21% at 10 µg mL-
1
, 9.37% at 20 µg mL-1, 15.25% at
40 µg mL-1) and cell cycle arrest in G2/
M phase;
6. Apoptosis was regulated by
increased expression levels of Fas (=
192% at 40 µg mL-1) and FasL (=
550% at 40 µg mL-1)
Eugenol Gastric carcinoma MNNG-induced cancer (eugenol at 100 mg kg-1 In vivo (in male 1. Reduction in tumour growth upon [162]
body weight) rats; 6–8-weeks- eugenol treatment (= 16.66%, tumour
old; weight = burden = 14.77 mm3);
80–100 g) 2. Expression levels of NF-κB, pIκBα,
IKKβ, cyclin D1, cyclin B, and PCNA
were reduced whereas increase in the
expression of IκBα, p21, p53 and
Gadd45 was observed
Eugenol Colon carcinoma (At 0–1500 µM eugenol for 48 h): HCT-15: IC50 In vitro 1. Anti-proliferative effect of eugenol [163]
= 300 µM, HT-29: IC50 = 500 µM was observed in the tested cancer cell
lines;
2. Arrest of cancer cells in sub-G1
phase of cell cycle (HCT-15:
7.92–37.84% and HT-29:
7.99–33.29% at 12–48 h);
3. Induction of apoptosis due to
decrease in MMP [= 74% (in HCT-15)
and 34% (in HT-29) after 6 h],
increase in p53 protein and activation
of caspases
Geranial, neral, and citral Mouse breast cancer 4T1 (at 72 h):Geranial-loaded micelles In vitro; 1. Autophagy of cells upon treatment [164]
(Geranial/NP): IC50 = 1.4 µM; Neral/NP: IC50 In vivo (in Balb/c for 48 h with 25 µM of neral/NP,
= 9.9 µM; Citral/NP: IC50 = 4.5 µM mice) citral/NP, and geranial/NP; geranial
exhibited more potent effect;
2. In vivo: at 40 and 80 mg kg-1:
decrease in tumour growth (C40, G40,
and N40: 32–49% reduction at 24th
day)
Geraniol Non-small cell In vitro: (At 0–1800 µM geraniol): A549: IC50 In vitro 1. Anti-proliferative effect of geraniol [165]
human pulmonary = 797.2 µM; In vivo (in nude was observed on cancer cells;
carcinoma In vivo: 25, 50, and 75 mmol geraniol kg-1 food mice) 2. Decrease in tumour growth
given to mice especially in mice receiving 50 and
75 mmol geraniol kg-1 food at day 14;
3. Increase in apoptosis and cell death
(at 50 mmol geraniol kg-1 food- treated
mice);
4. Decrease in cholesterol levels by
about 55% in cancer cells
Geraniol Colon carcinoma In vitro: (At 50–400 µM) Murine endothelial- In vitro 1. Increase in apoptosis and necrosis; [166]
like eEND2 cells, HDMEC; In vivo (in BALB/ 2. Cell migration was reduced in
In vivo: CT26 c mouse) eEND2 cells;
3. Tumour growth rate was decreased
in geraniol-treated mice (tumour size
= ~3 mm2 at 14th day);
4. Decrease in expression of VEGF,
thus promoting anti-angiogenesis
Geraniol Human hepatoma, (At 50–800 µM geraniol): HepG2, A549 In vitro 1. Antioxidant mechanism contributed [167]
Human lung to the anticancer effect of geraniol;
adenocarcinoma 2. Decrease in cell viability (HepG2:
17.9–38.3% and A549: 24.7–47.4% at
200–800 µM geraniol);
19
3. Cell growth inhibition and cell cycle

arrest in G0/G1 interphase (at 200 and
800 µM) and G2/M arrest (by 50 µM
geraniol);
4. Increase in lipoperoxidation at
200 µM geraniol (HepG2: TBARS =
33%, A549: TBARS = 122%);
5. Decline in SOD and CAT enzymes by
44% and 30% at 200 µM geraniol in
HepG2 cells;
6. Increase in ROS levels by 46% and
99% at 200 and 800 µM geraniol in
HepG2 cells
Germacrene D; Murine melanoma, (Combination of germacrene D and In vitro Cytotoxic effect of various [168]
Bicyclogermacrene Colon carcinoma, bicyclogermacrene): B16F10-Nex2: IC50 concentrations of germacrene D and
Leukemia = 2.8 ± 0.1–8 ± 1 µg mL-1, HCT: IC50 bicyclogermacrene was observed in
= 2.7 ± 0.2–7 ± 1 µg mL-1, HL-60: IC50 the tested cell lines
= 2.7 ± 0.0–4.4 ± 0.5 µg mL-1
Globularifolin Glioma (At 0.75–200 µM globularifolin for 48 h): U87: In vitro 1. Decrease in cell viability; [169]
IC50 = 7.5 µM In vivo (in female 2. Induction of apoptosis (% apoptotic
nude mice; 6- cells = 15% at 15 µM) as a result of
week-old) increased expression of caspases, Bax,
cytochrome c, decrease in Bid protein,
and inhibition of Akt and phospho-
ERK;
3. Arrest of cancer cells in S phase of
cell cycle from 3.52 to 15 µM
globularifolin;
4. Increased ROS production at 3.52,
7.5, and 15 µM;
5. Inhibition of cell migration and
invasion (at 1–3 µM for 24 h) due to
decreased expression of MMPs;
6. In vivo: Decrease in tumour growth
and volume after 4 weeks
globularifolin at 25 mg kg-1 body
weight
Hinokitiol Mouse melanoma In vitro (At 1, 2, 5, and 10 µM hinokitiol for 24 In vitro 1. Cytotoxicity in cancer cells (at [170]
and 48 h): B16-F10; In vivo (in 10 µM);
In vivo: 10–20 µg mouse-1 hinokitiol C57BL/6 mice) 2. Decreased levels of MMPs (at 5 µM
hinokitiol);
3. Decrease in cancer cell migration;
4. Decreased expression of p38, ERK1/
2, and phosphorylation of JNK1/2
(50% decline at 5 µM);
5. In vivo: Decreased formation of
tumour nodules (= 42.10% and 65.5%
at 10 and 20 µg mouse-1 hinokitiol,
respectively)
Hinokitiol Human lung (At 20–100 µM for 24 h): A549 In vitro 1. Reduction in cell viability; [171]
adenocarcinoma 2. Inhibition of cancer cell migration
(at 5 µM) due to decreased expression
of MMPs;
3. Induction of apoptosis due to
increased expression of p53, Bax,
caspases (3 and 9), and cytochrome c;
4. Increase in antioxidant enzymes
(CAT and SOD) at 2 and 5 µM
Hinokitiol Metastatic (At 1–20 µM): B16-F10 In vitro 1. After 14 days, decrease in colony [172]
melanoma formation (= 21 ± 6 at 5 µM and 3 ± 2
at 20 µM);
(observations: condensation of
chromatin and nuclei) due to
decreased expression of survivin (an
anti-apoptotic protein) at 5–40 µM
hinokitiol for 24 h, decrease in ERK
phosphorylation, and increased
expression of MAPK phosphatase-3;
3. Reduced cell migration (=
53.2 ± 6% at 10 µM)
Jatamanvaltrate P Human breast cancer In vitro (At 0–50 µM): MDA-MB-231: IC50 In vitro 1. Reduction in cell viability due to [173]
= 4.32 ± 1.34 µM, MDA-MB-468: IC50 In vivo (in BALB/ anti-proliferative effect;
= 7.05 ± 2.51 µM, MDA-MB-453: IC50 c nude female 2. Increase in the number of apoptotic
= 4.05 ± 0.18 µM, MCF-7: IC50 cells (at 2.5 and 5 µM for 24 h) due to
20
= 5.59 ± 1.21 µM, MCF-10A: IC50 mice; 4-week- increased cleavage of caspases and
= 41.39 ± 3.92 µM; old) PARP;
In vivo: At 15 mg kg-1 Jatamanvaltrate P (3 3. Arrest of cancer cells in G2/M phase
times/week for 30 days) in all except MCF-7 in G0/G1 phase;
4. Autophagy was also induced as
revealed by increase in LC3-II/LC3-I
ratio (at 2.5 and 5 µM);
5. In vivo: Decrease in tumour growth
(= 49.7% on day 30)
D-Limonene Human colon cancer LS174T In vitro 1. Reduction in cell viability (at [174]
0.1–3.2 mmol L-1 D-limonene for
48 h);
2. Increased apoptosis via cleavage of
caspases (3 and 9) and up-regulation of
Bax and down-regulation of Bcl-2
protein
Limonene Human bladder Cell cytotoxicity (At 0–320 µM limonene for In vitro 1. Increase in cancer cell cytotoxicity [175]
cancer 24 h): T24: IC50 = 9.0 µM; with increasing concentrations of
Apoptosis (At 0–36 µM limonene for 24 h): T24 limonene;
2. Induction of apoptosis (% apoptotic
cells = 5.35%––34.71% at 9–36 µM
limonene);
3. Up-regulation of Bax, cleavage of
caspases (3 and 9), and down-
regulation of Bcl-2;
4. Cell cycle arrest in G2/M phase
(73% cells at 36 µM limonene);
5. Decreased cancer cell migration and
invasion
Limonene Human (At 0.0006–0.86 mg mL-1 for 72 h): HepG2: In vitro Anti-proliferative activity of limonene [55]
hepatocellular EC50 = 0.42 ± 0.017 µM, Caco2: EC50 was observed against the tested cell
carcinoma, = 0.09 ± 0.0042 µM, A375: EC50 lines
Colon = 0.0098 ± 0.001 µM
adenocarcinoma,
Malignant
melanoma
Linalool Human colorectal (At 0–1000 µmol L-1 for 24 h) In vitro: HCT 116, In vitro 1. Anti-proliferative effect of linalool [176]
carcinoma, WiDr, HCT-15, SW480, RKO; In vivo (in male (at 250 µmol L-1);
Human colon In vivo: At 100 and 200 mg kg-1 linalool (every mice; 6-week- 2. Increase in cytotoxicity with
carcinoma 3rd day for 21 days) old) increasing concentrations of linalool;
3. Increased apoptosis (observations:
chromatin fragmentation, shrunken
cells) and % apoptotic cells (=
10.5 ± 7.7% when treated with
100 µmol L-1 linalool);
4. Reduction in tumour weight and
size (especially at 200 mg kg-1
linalool)
Linalool Human (At 0–2.5 mM linalool for 24 and 48 h): HepG2 In vitro 1. Reduced cell viability and anti- [177]
hepatocarcinoma (HB-8065) proliferative effect of linalool (at 72 h
of 0.5 mM linalool and 24–48 h of
1.0 mM linalool);
2. Arrest of cancer cells in G0/G1
phase of cell cycle after 24 and 48 h
(especially from 1.0 mM);
3. Increased apoptosis through up-
regulation of caspases (especially at
1.5 and 2.0 mM for 48 h) and % of
apoptotic nuclei (= 5.77% and 10.04%
at 1.5 and 2.0 mM for 48 h);
4. Increased ROS levels synergistically
added to the anti-proliferation ability
of linalool;
5. Inhibition of ERK protein decreased
cancer cell viability to 8% at 2.0 mM
linalool;
6. Inhibition of phosphorylation of Akt
protein decreased cell viability to
12.3% upon combined treatment of
linalool and Ly (an Akt
phosphorylation inhibitor)
Linalool Human epidermoid HEP2: IC50 = 25.23 ± 2.3 µM, PC-3: IC50 In vitro Reduction in cancer cell viability [178]
carcinoma, = 46.01 ± 3.4 µM
Prostate cancer
In vitro [179]
21
Linalool; Human lung A549: IC50 = 141.76 ± 14.59 µg mL-1 (for Cancer cell proliferation was inhibited
3-Carene; adenocarcinoma linalool), IC50 = 70.80 ± 8.24 µg mL-1 (for 3- by all the constituents tested
α-Terpineol; carene), IC50 = 51.37 ± 4.92 µg mL-1 (for
Decanal; Citral; α-terpineol), IC50 = 37.10 ± 2.96 µg mL-1 (for
D-Limonene; decanal), IC50 = 35.15 ± 2.38 µg mL-1 (for
α-Pinene citral), IC50 = 22.10 ± 1.94 µg mL-1 (for D-
limonene), IC50 = 22.01 ± 1.75 µg mL-1 (for
α-pinene)
Myristicin Human leukemia (At 50–1000 μM for 24, 48, and 72 h): K562: In vitro 1. Decrease in cell viability (= >20% [180]
IC50 = 368 µM at 500 µM for 24/48 h and >50% at
concentrations >250 µM for 72 h);
2. Induction of apoptosis through
cytochrome c release (at 6 h), caspase-
3 activation (especially at 250 and
500 µM for 48/72 h), increase in PARP
cleavage;
3. Decreased expression of genes such
as ATM (involved in DNA damage
signalling), RAD50, RAD51 (involved
in DNA repair), ERCC1 (involved in
repair of nucleotide excision),
GADD45A, GADD45G (involved in
stress response)
Myrtenal Murine melanoma, (At 10–200 µM myrtenal for 24 h): B16F0, In vitro 1. Reduction in cell viability (= [181]
Metastatic human B16F10, SkMel-5; In vivo (in 40–50%) especially at 100–200 µM in
melanoma In vivo: At 15 mg kg-1 myrtenal; 21 days C57BL-6 mice; B16F10 and SkMel-5);
6–8-weeks-old) 2. Induction of cell death (at
12–50 µM) and apoptosis (chromatin
condensation, nuclear fragmentation);
3. Cell death (= 80% in SkMel-5 and 4-
fold increase in case of B16F0 and
B16F10);
4. Decrease in cancer cell migration at
5–10 µM;
5. In vivo: Decrease in tumour
progression and tumour nodules
formation
Neem oil limonoids Colon cancer, HCT116, LNCaP, PPC1, MDA-MB-231 In vitro 1. Increased apoptosis and cell death in [182]
Prostate cancer, all the cancer cell lines tested;
Breast cancer 2. Autophagy was also induced due to
the expression of LC3-I and LC3-II;
3. Increase in caspase-3 activity and
mitochondrial cytochrome c whereas
PI3K/AKT pathway was inhibited and
p21 protein expression was also
decreased
Nimbolide Human colorectal HCT-116, HT-29, Caco-2 In vitro 1. Proliferation of cancer cells was [183]
cancer In vivo largely inhibited and cytotoxicity was
(in athymic observed at 10 µmol L-1 nimbolide
nude mice; 4- (HCT-116 = 52.5%, HT-29 = 38.4%,
weeks-old) and Caco-2 = 43.1%);
2. Induction of apoptosis via increase
in caspases and cleavage of PARP;
3. Decreased expression of Bcl-2, Bcl-
xL, survivin, and c-IAP-1 (anti-
apoptotic proteins) and cyclin D1 and
c-Myc (cell proliferation proteins);
4. Inhibition of activation of NF-κB and
IκBα phosphorylation;
5. Decreased tumour growth (90% at
20 mg kg-1 body weight at 10th day)
Nimbolide Human (At 0–6 µM for 24 h): HepG2: IC50 = 5 µM In vitro 1. Inhibition of cancer cell [184]
hepatocarcinoma proliferation;
2. Increase in the expression levels of
IκBα while decreased expression of NF-
κB-p50 and p65, pIκB-α, IKKβ, GSK-3β,
and β-catenin;
3. Induction of apoptosis (features:
condensed chromatin, fragmented
DNA, membrane convulsions) due to
increase in Bax protein, cytochrome c
release, and activation of caspases
whereas decreased expression of Bcl-2
Oleuropein Human (At 25–800 µM oleuropein for 72 h): SH-SY5Y: In vitro 1. Decrease in cell viability with [185]
neuroblastoma IC50 = 350 µM at 48 h increasing concentrations and time;
22
2. Increase in apoptosis genes (such as

Bax, caspases) and decrease in Bcl-2
expression and % of apoptotic cells (=
36.4 ± 3.27%);
3. Inhibition of cancer cell invasion (by
41.46 ± 2.04%) and decrease in
colony formation (= 19 ± 1)
Patchouli alcohol Human colorectal (At 0–100 µM for 24 and 48 h): HCT116, In vitro 1. Cell proliferation decreased (by [186]
cancer, SW480, MCF-7, BxPC3, PC3 22–56% and 18–46% in HCT116,
Breast cancer, 19–69% and 31–88% in SW480 at 24
Pancreatic cancer, and 48 h when treated with 50–75 µM,
Prostate cancer respectively) and a decrease of 24%
and 59% (at 24 h), 36% and 76% (at
48 h) in MCF-7 cells, 28% and 49% (at
24 h), 54% and 65% (at 48 h) in PC3
upon treatment with 75 and 100 µM;
2. Expression of proteins involved in
cell cycle (= decrease in cyclin D1,
CDK4, and c-myc but increase in p21)
in HCT116 and SW480 cells;
3. Induction of apoptosis by activation
of NF-κB and nuclear translocation of
p65 in HCT116 and SW480 cells
Perillyl alcohol Human cervical (At 5–200 µM for 24 h): HeLa, SK-Hep1, In vitro 1. Decrease in cell viability; [187]
cancer, HCT116; In vivo (in Crj: 2. Arrest of cancer cells in G1 phase of
Hepatic cancer, In vivo: At 50 and 100 mg kg-1 BALB/c nude cell cycle at 200 µM (= 69.41%)
Colon cancer male mice; 5- through increased expression of p21
weeks-old) and p53 proteins and decrease in
cyclin D1, c-Myc, and Skp2;
3. In vivo: Reduction in tumour growth
(= 64.11% at 200 mg kg-1)
Perillyl alcohol; Human colon (− )-Perillaldehyde 8,9-epoxide: HCT-116: IC50 In vitro 1. Anti-proliferative effect of perillyl [188]
(− )-Perillaldehyde 8,9- carcinoma, = 1.03 µg mL-1, OVCAR-8: IC50 = 1.15 µg mL-1, alcohol;
epoxide Ovarian SF-295: IC50 = 1.75 µg mL-1, HL-60: IC50 2. Cell growth inhibition by perillyl
adenocarcinoma, = 0.64 µg mL-1 alcohol (= 95.82 ± 0.30% in HCT-
Glioblastoma, 116, 91.68 ± 7.06% in OVCAR-8, and
Leukemia 90.92 ± 0.39% in SF-295);
3. Induction of apoptosis and necrosis
by (− )-Perillaldehyde 8,9-epoxide
(observable features: condensed
chromatin, fragmented nuclei, swollen
cells)
Perillyl alcohol; Human lung (Dehydroperillic acid): A549: IC50 In vitro Cytotoxicity of perillyl alcohol and its [189]
Dehydroperillic acid (a carcinoma, = 125 µg mL-1, metabolite was observed against tested
metabolite of perillyl Hepatocarcinoma (Perillyl alcohol): HepG2: IC50 = 409.2 µg mL-1 cancer cell lines
alcohol)
α-Santalol Breast cancer (At 10–100 µM): MCF-7, MDA-MB-231 In vitro 1. Cell viability was reduced (in MCF-7 [190]
by 2–38% at 12 h, 2–58% at 24 h,
4–71% at 48 h and in MDA-MB-231 by
1–47% at 12 h, 2–66% at 24 h, 4–79%
at 48 h);
2. Cell proliferation was reduced (at
12, 24, and 48 h, respectively: MCF-
7 = 1–49.5%, 4–89%, and 10–93%,
MDA-MB-231 = 0–50%, 4–69% and
3–85%);
3. Arrest of cancer cells in G2/M phase
due to decrease in expression levels of
cyclin A, CDK2, and Cdc2;
4. Increased apoptosis due to the
activation of caspases and PARP
cleavage;
5. Down-regulation p53 whereas up-
regulation of p21 (an inhibitor of CDK)
protein
4-Terpineol Hepatocellular (At 0–100 µM 4-terpineol for 24 h): HepG2: In vitro 1. Increase in cytotoxicity with [191]
carcinoma IC50 = 19.5 µM In vivo (in 6- increasing concentrations of 4-
week-old BALB/ terpineol;
c nude female 2. Induction of cell death and
mice) apoptosis as revealed by DNA
fragmentation (% apoptotic cells =
10.3%––78.9% at 25–100 µM 4-
terpineol);
3. Inhibition of cancer cell migration
and invasion as observed by complete
23
closure of wound scratch after 48 h

treatment;
4. Cell cycle arrest in sub-G1 phase;
5. Decrease in tumour weight
[= 0.91 g and 0.42 g, respectively (at
10 and 20 mg kg-1 4-terpineol)] and
tumour volume [= 0.75 cm3 and
0.26 cm3, respectively (at 10 and
20 mg kg-1 4-terpineol)
α-Thujone, 1,8-cineole, Prostate cancer, LNCaP, MCF-7, HeLa: at 50, 100, and In vitro 1. Reduction in cell viability at 100 [114]
and camphor (mixture) Breast cancer, 200 µg mL-1 for 24, 48, and 72 h and 200 µg mL-1 after 48 h incubation;
Cervical cancer 2. 100 µg mL-1: Cytotoxic to MCF-7
and HeLa cancer cells;
3. 200 µg mL-1: Cytostatic to LNCaP
cancer cells
α-Thujone Glioblastoma (At 10–500 µg mL-1 α-thujone): T98G, U87, In vitro 1. T98G: swollen cells and necrosis (at [192]
multiforme Mouse astrocytes (C8-D1A) 250 and 500 µg mL-1 α-thujone,
respectively), U87: cytotoxic effect;
2. Antioxidant mechanism was
responsible for the observed
anticancer effect;
3. Increase in apoptosis and necrosis;
4. Autophagy was observed in T98G
cells at 250 µg mL-1 α-thujone from 4
to 24 h incubation time;
5. Inhibition of T98G cell migration
especially at 100 and 250 µg mL-1
α-thujone
Thymol Oral squamous cell Cal27, SCC4, SCC9, HeLa, H460, MDA-231, In vitro 1. Decreased cell viability with GC50 s [193]
carcinoma, PC3; In vivo (in nude = 300–550 µmol L-1 in all the cell lines
Cervical cancer, In vivo: At 4.3 mmol L-1 thymol female mice; 6- tested;
Non-small cell lung week-old) 2. Cytotoxic to Cal27 and HeLa cell
cancer, lines and formation of no colonies after
Breast cancer, 9 days (at 4.3 mmol L-1 thymol);
Prostate cancer 3. In vivo: Decrease in tumour volume
at 16th day (= 96 mm3 in Cal27 and
537 mm3 in HeLa); presence of large
number of apoptotic and necrotic cells
Thymol Human gastric (At 10–400 pM thymol): AGS: IC50 In vitro 1. Reduced cell viability (= 87.8% at [194]
adenocarcinoma = 75.63 ± 4.01 pM 30 pM and 0.66% at 600 pM);
2. Increased ROS production and
decline in GSH levels;
3. Induction of apoptosis and necrosis
(features: shrunken nucleus,
condensed chromatin) and higher
number of apoptotic cells (at 20–100
pM) and necrotic (30–100 pM) cells
were observed;
4. Apoptosis was also regulated by
increase in the expression levels of
caspases (3 and 9) and Bax, and
decrease in Bcl-2 protein
Thymol Acute promyelotic (At 5–100 µM for 24 h): HL-60 In vitro 1. Decrease in cell viability (especially [195]
leukemia from 25 µM after 24 h);
2. Cell cycle arrest at G0/G1 phase;
3. Increased ROS levels (at
25–100 µM);
4. Increase in apoptosis due to
activation of caspases (3, 8, and 9)
after 24 h, up-regulation of Bax, and
down-regulation of Bcl-2
Thymol Neuroblastoma (At 0–400 mg L-1): N2a In vitro Reduction in cell viability (especially [196]
at 200 and 400 mg L-1)
Thymol; Breast cancer Cytotoxicity: MDA-MB-231: IC50 = 149 µg mL- In vitro 1. Anti-proliferative activity of thymol [197]
1
Carvacrol; , (MDA-MB-231: IC50 = 56 µg mL-1,
p-Cymene MCF-7: IC50 = 134.5 µg mL-1 MCF-7: IC50 = 47 µg mL-1), carvacrol
(MDA-MB-231: IC50 = 53 µg mL-1,
MCF-7: IC50 = 46.5 µg mL-1), and p-
cymene (MDA-MB-231: IC50 =
295.2 µg mL-1,
MCF-7: IC50 = 261 µg mL-1) was
observed;
2. Induction of apoptosis (as observed
by vacuolation in cytoplasm, round,
detached, shrunken, and floating cells)
24
and increase in activity of caspases and

increase in Bax/Bcl-2 ratio;
3. Increased ROS levels may contribute
to cell death;
4. Arrest of cancer cells in the S phase
of cell cycle by thymol at 4 and 12 h
Abbreviations: PARP: poly-ADP ribose polymerase, Bax: Bcl-2-associated X protein (apoptosis regulator), Bcl: B-cell lymphoma 2, AKT: a serine-threonine specific
protein kinase, ERK: extracellular-signal-regulated kinase, JNK: c-jun N-terminal kinase, KISS1R: kisspeptin, a G protein-coupled receptor, TIMP2: tissue inhibitor of
metalloproteinase 2, HmgB1: high mobility group box 1 protein, ROS: reactive oxygen species, GSH: glutathione, mTOR: mechanistic target of rapamycin, S6K1:
ribosomal S6 kinase 1, PI3K: phosphoinositide 3-kinase, MAPK: mitogen-activated protein kinase, BAK: Bcl-2 homologous antagonist/killer, CDK2: cyclin-dependent
kinase 2, MEK: mitogen-activated protein kinase kinase, cdc25c: cell division cycle 25c, VEGF: vascular endothelial growth factor, LC3: microtubule-associated protein
light chain 3, Atg5: autophagy related 5, Atg12: autophagy related 12, Fas: FS-7-associated surface antigen, FasL: Fas ligand, NF-κB: nuclear factor kappa-light-chain-
enhancer of activated B cells, pIκBα: inhibitor of NF-κB alpha (phosphorylated form), IKKβ: inhibitor of nuclear factor kappa-B kinase subunit beta, PCNA: proliferating
cell nuclear antigen, Gadd45: growth arrest and DNA damage-inducible 45, TBARS: thiobarbituric acid reactive species, SOD: superoxide dismutase, CAT: catalase,
Bid: BH3-interacting domain death agonist, ATM: ataxia-telangiectasia mutated kinase, ERCC1: excision repair cross complementation group 1, c-IAP-1: cellular
inhibitor of apoptosis protein-1, GSK-3β: glycogen synthase kinase 3 beta, Skp2: S-phase kinase associated protein 2.
proteins such as Bax (Bcl-2-associated X protein, apoptosis regulator) growth was suppressed in mice (at 50 and 75 mmol geraniol kg-1 food)
and caspases with a concomitant decrease in Bcl-2 (B-cell lymphoma 2) due to apoptosis and cell death [165]. Globularifolin iridoid exhibited
expression [137,140]. Citral exhibited antitumour effects in various cytotoxicity against U87 glioma cells because of increase in the number
cancer cell lines such as MDA-MB-231 [144], Ishikawa [145], ECC-1 of apoptotic cells, cell cycle arrest, and inhibition of cancer cell migra
[145], LNCaP [65], PC-3 [65], SF-767 [65], SF-763 [65], LU134AM tion and invasion [169]. Modulation in the activity of various proteins
[146], LU135 [146], LU165 [146], MN1112 [146], HCT116 [147], such as Bax, Bid (BH3-interacting domain death agonist), caspases, Akt,
HT-29 [147], AGS [148], NB4 [149], and A431 [151]. A combination phospho-ERK (extracellular-signal-regulated kinase), cytochrome c, and
formulation of citral (80 μM) and curcumin (40 μM) also acted syner matrix metalloproteinases (MMPs) favoured apoptosis in cancer cells
gistically in suppressing the growth of MCF-7 and MDA-MB-231 breast [169]. In vitro cytotoxicity of hinokitiol (a tropolone monoterpenoid)
cancer cell lines by inducing apoptosis, DNA damage, and cell cycle was observed (at 10 µM) in mouse melanoma cells (B16-F10); however,
arrest in G0/G1 phase [155]. In vitro/in vivo cytotoxic potential of under in vivo conditions, mice treated with 10–20 µg mouse-1 hinokitiol
citronellol has been reported against human non-small cell lung cancer exhibited reduction in tumour nodules [170]. The increased expression
(NSCLC) [156], breast cancer [156,157], and prostate cancer [156]. of p53 (a tumour suppressor), Bax, caspases, cytochrome c, and MAPK
Citronellol induced cell cycle arrest in NCI-H1299 (a NSCLC cell line) (mitogen-activated protein kinase) phosphatase-3, and down-regulation
due to the increased expression of cyclins (cyclin D and E) and CDK2 of survivin (an apoptosis inhibitor), MMPs, and ERK phosphorylation
(cyclin-dependent kinase 2) [156]. A decrease in tumour volume was has been reported to induce apoptosis in hinokitiol-treated A549 and
observed in mice treated with increasing doses of citronellol (12.5, 25, B16-F10 cells [170–172]. Similarly, treatment with linalool (a mono
and 50 mg kg-1) [156]. Anti-proliferative effect of geraniol (a mono terpene alcohol) decreased the proliferation and cell viability in colo
terpenoid) was observed in A549 cells (IC50 = 797.2 µM) and tumour rectal carcinoma [176], colon carcinoma [176], hepatocarcinoma
Fig. 4. The role of essential-oil based aromatherapy in strengthening immunity and producing anti-stress effects.
25
Table 3 Table 3 (continued )

A list of important essential oils and their therapeutic applications during cancer Essential oil Major constituent Therapeutic Reference
suppressive aromatherapy. source (Plant (s) properties and (s)
Essential oil Major constituent Therapeutic Reference name, Plant benefits in
source (Plant (s) properties and (s) family) aromatherapy
name, Plant benefits in infections,
family) aromatherapy regulates diabetes,
Salvia sclarea L. Linalool, linalyl 1. Used as a tonic for [198,203, relieves
(Lamiaceae) acetate, uterus and womb- 204] menopause-
α-terpineol, geranyl, associated associated
germacrene D problems; problems;
2. Regulation of 6. Relieves pain and
menstrual periods supports therapy in
and easing of cancers of the
cramps; breast and uterus;
3. Sleep-inducing and 7. Insect repellent;
aphrodisiac 8. Anti-diabetic,
activities; antimicrobial, and
4. Controls sebum and anticancer
cellulite production properties
and can be used for Lavandula Camphor, terpinen- 1. Calming effect on [200,
both oily and dry officinalis Chaix 4-ol, the nervous system 211–213]
skin, acne, (Lamiaceae) 1,8-cineole, as it absorbs greatly
wrinkles; β-ocimene, linalool, through the skin
5. Antimicrobial linalyl acetate during massage
activity; aromatherapy;
6. Controls cortisol 2. Lavender pillows
levels in women help in relieving
Eucalyptus Cineole, 1. Regulation and [200,205, anxiety and
globulus Labill. aromadendrene, activation of 206] aggression, and
(Myrtaceae) limonene, terpinene, nervous system; improves alertness
cymene, 2. Boosts immune in patients
phellandrene, system during cold, suffering from
pinene measles, flu, and sleep disturbance
chickenpox; problems;
3. Finds use in the 3. Antibacterial and
treatment of antifungal
leucorrhea and properties;
genitourinary 4. Used in the
system-associated treatment of burns,
cystitis; abrasions,
4. Respiratory headache, stress,
infections (throat, skin diseases,
cough, sinusitis, muscular pains;
bronchitis, 5. Promotes the
asthma); growth of new cells
5. Skin infections and boosts immune
(herpes, cuts, system;
wounds, burns, 6. Finds use in the
lice, insect bites); treatment of
6. Insect repellent; dysmenorrhea
7. Treatment of Citrus limon (L.) D-limonene, 1. Antiseptic, [200,
muscle and joint Osbeck, L-limonene, detoxification of 214–216]
pains, rheumatoid Citrus phellandrene, blemishes, and
arthritis; aurantium L., pinene, citral astringent
8. Antioxidant, anti- Citrus bergamia properties;
proliferative, anti- Risso & Poit. 2. Restoring the skin
inflammatory, and (Rutaceae) lustre;
antibacterial 3. Immune system
Pelargonium Geranic, eugenol, 1. Natural perfume, [200, enhancement along
graveolens L′ linalool, geraniol, also used in soaps 207–210] with counteraction
Hér. citronellol, and detergents; of acidity,
(Geraniaceae) citronellyl formate, 2. Controls emotions, treatment of ulcers,
myrtenol, terpineol, anxiety, and stress improvement of
citral, sabinene, during digestion;
methone aromatherapy; 4. Helps in relieving
3. Skin problems labour pains
(dermatitis, fungal (generally at stage
infections, ageing I);
skin, eczema); 5. Prevents nausea
4. Antibacterial and vomiting, and
activity and used in also enhances
the treatment of mood
endometriosis; Mentha piperita L. Carvacrol, menthol, 1. Relieves pain, [200]
5. Acts as a sedative, (Lamiaceae) carvone, methyl spasms,
stimulates nerves, acetate, menthone, stomachache,
treats throat limonene headache, arthritis;
26
Table 3 (continued ) Table 3 (continued )

Essential oil Major constituent Therapeutic Reference Essential oil Major constituent Therapeutic Reference
source (Plant (s) properties and (s) source (Plant (s) properties and (s)
name, Plant benefits in name, Plant benefits in
family) aromatherapy family) aromatherapy
2. Anti-inflammatory, 5. Stimulates nervous

antiseptic, system and
antimicrobial, prevents paralysis
astringent, and hysteria;
fungicidal, nerve 6. Can improve
stimulant, dementia and
decongestant cognitive abilities
properties; in patients
3. Relieves pain suffering from
during Alzheimer’s disease
menstruation and using
also used in aromatherapy;
treating irritable 7. Eases menstrual
bowels; cramps
4. Relieves skin Melaleuca Terpinen-4-ol, 1. Enhances immune [200,217,
irritation during alternifolia α-sabinene, cineole system; 218]
herpes blisters, (Maiden & 2. Used in the
infestation of Betche) Cheel treatment of
ringworm, poison (Myrtaceae) abscess, burns, cold
ivy, poison oak, sores, herpes,
and scabies; insect bites, acne
5. Finds application blisters;
as a vapour balm; 3. Treatment of
6. Acts as a respiratory
decongestant and infections (asthma,
relieves sinus; tuberculosis,
7. Antibacterial, bronchitis, cough)
antiviral, and and herpes;
antifungal 4. Treatment of
properties vaginitis, pruritus,
Anthemis nobilis L. Angelic acid esters, 1. Finds use in the [200] and cystitis in
(Asteraceae) tiglic acid, 2-meth treatment of hay women;
ylbutanoic acid fever, ulcers, 5. Treatment of flu,
rheumatic and fever, cold, and
gastrointestinal chicken pox
disorders, muscle Cananga odorata Geranyl acetate, 1. Relieves depression [200,219]
spasms, menstrual (Lam.) Hook.f. β-caryophyllene, and promotes
problems, & Thomson methyl chavicol, euphoria;
headache, (Annonaceae) geraniol, eugenol, 2. Increases self-
depression, and geranial, linalool, esteem and post-
wounds; pinene, farnesol, menopausal prob
2. Relieves stress and farnesene, benzyl lems in women;
anxiety and its acetate 3. Aphrodisiac
anxiolytic property on both
properties aid in dry and oily skin;
aromatherapy; 4. Relieves anxiety,
3. Relaxes mind and high blood
aids in peaceful pressure, stress,
sleep; and palpitations
4. Relieves menstrual
cramps and eases
tension; [177], epidermoid carcinoma [178], and prostate cancer [178]. Diallyl
5. Treatment of skin disulphide (DADS), one of the major components of garlic EO, arrested
infections
(psoriasis, sunburn,
the division of human esophageal squamous cancer cells at G2/M phase
boils, eczema, cold of cell cycle [158]. Myristicin, an active component of Myristica fragrans
sores); Houtt. EO, exhibited cytotoxic activity by inducing apoptosis of K562
6. Reduces joint pains human leukemia cells [180].
and pain associated
Various other EO constituents such as bakuchiol (a monoterpene)
with stings
Rosmarinus Bornyl acetate, 1. Improves digestion [200] [133], myrtenal (a bicyclic monoterpene) [181], oleuropein (a
officinalis L. borneol, camphor, and relieves seco-iridoid) [185], perillyl alcohol (a mentan monoterpene)
(Lamiaceae) pinene, camphene, constipation and [187–189], thymol (a monocyclic phenolic monoterpene) [193–197],
cineole colitis; α-bisabolol (a monocyclic sesquiterpene alcohol) [134,135], α-thujone
2. Maintains healthy
liver and gall
(a ketone monoterpene) [114,192], camphene (a bicyclic monoterpene)
bladder; [105], jatamanvaltrate P (an iridoid ester) [173], eugenol (a phenyl
3. Regulates blood propanoid) [141,162,163], germacrene D (a sesquiterpene) [168],
pressure and delays nimbolide (a terpenoid lactone) [183,184], patchouli alcohol (a
hardening of
sesquiterpene alcohol) [186], α-santalol (a sesquiterpene) [190], car
arteries;
4. Relieves rheumatic veol (a monocyclic monoterpenoid alcohol) [141], carvone (a mono
pain during cold; terpene) [141], isopulegol (a monoterpene alcohol) [141],
β-caryophyllene oxide (a bicyclic sesquiterpene) [143], and β-elemene
27
Fig. 5. Illustration of the various intravenous essential oil-loaded drug delivery systems for targeting cancer cell cytotoxicity.
(a sesquiterpenoid oxide) [159–161] have also been reported as cyto increasing temperature beyond 10 ◦ C, degradation of active EO sub
toxic and anti-proliferative compounds with anticancer effects. stances during digestion or undesirable metabolic transformation by
enzymes, and ineffective absorption/elimination by excretion, it is
deemed necessary to properly design a therapeutic window of EOs to
3.3. Tools for supportive anticancer therapies and effective EO delivery in maximize their widespread application [221]. Studies have reported
living systems that EOs are effective between 2 and 5 h of administration. For example,
active components of certain EOs such as thymol and carvacrol exhibi
3.3.1. Aromatherapy: the roots of a bio-based solution to enhance ted plasma half-lives between 1.47 and 1.51 h, and tissue half-lives
immunity against cancer ranged between 13.9–31.5 and 16.9–25.0 h, respectively [222]. Thus,
The ongoing use of aromatherapy using EOs is part of an integrated for therapeutic activity of EOs, an effective delivery to the target cell is
treatment approach to cancer and palliative care. Aromatherapy is pri required. EOs reportedly have irritating properties in the body and body
marily used as a pain-relieving tool to help people cope up with stress enzymes might inactivate them upon recognizing as foreign compounds.
and anxiety, thus aiding in rejuvenation and regeneration of the body These hindrances can be overcome by using an efficient drug delivery
[198] (Fig. 4). For example, patients diagnosed with cardiovascular system using lipids, glycerol, microcapsules/nanocapsules, liposomes,
problems, Alzheimer’s disease, sleep disorders, and cancers can benefit nanostructured lipid carriers, and solid lipid carriers [223–226] (Fig. 5)
from aromatherapy and evade emotional stress [198]. Aromatherapy Encapsulation of EOs in drug delivery system decreases volatility and
conditions the immune system by alleviating stress levels, controlling toxicity and improves stability, bioavailability, and biological activity of
hormonal secretions from adrenal glands, inducing detoxification by EOs [225]. For instance, cyclodextrin (a derivative of starch) has been
lymph tissues, and removing the microorganisms from body [21] used to enclose EOs in polymeric nanoparticles for better availability
(Fig. 4). Various EOs obtained from tea tree, clove, eucalyptus, thyme, and stability [227]. Effective administration of EOs can also be achieved
and lavender are reported to enhance the immune response using by microencapsulation using natural polymers [228], semi-synthetic
aromatherapy [199]. A blend of coconut (Cocos nucifera L.) and ginger polymers [224] or porous membrane vesicles [229]. Polyethylene gly
(Zingiber officinale Roscoe) EO was effective in raising immunity, when col (PEG) polymeric nanoparticles loaded with geranium or bergamot
massaged on colorectal cancer patients receiving chemotherapy [200]. EOs are synthetic polymers that exhibited larvicidal activity against
Similarly, the use of EOs of lavender (Lavandula angustifolia Mill.), Culex pipiens [227]. Similarly, nanospheres of Zanthoxylum rhoifolium
peppermint (Mentha piperita L.), orange (Citrus sinensis [L.] Osbeck), and Lam. [230] and Rosmarinus officinalis L. [231] EOs exhibited insecticidal
frankincense (Boswellia carteri Birdw.) might produce relaxing and activity against Bemisia tabaci and Tribolium castaneum, respectively.
calming effects in cancer patients during chemotherapy/radiation In the past, formulation strategies such as nano-sized NDDS (novel
therapy [201, 202]. EOs and their therapeutic applications during can drug delivery system), chitosan-alginate nanoencapsulation, and self-
cer suppressive aromatherapy are detailed in Table 3. emulsifying microspheres were used to increase stability and absorp
tion of EOs [232,233]. For example, clove, lemon or eucalyptus EOs
3.3.2. Knowledge of cancer cell specificity and drug delivery strategies loaded in niosomes were effective in enhancing transdermal delivery of
impact EO activity felodipine drug [234]. Co-encapsulation of Nigella sativa L. EO and
A clear picture of the pharmacokinetic profile of EOs is critical for indomethacin poly (ε-caprolactone) nanoparticles improved the
understanding their efficacy and toxicity. Thus far, despite an array of anti-inflammatory properties of indomethacin in a human skin model
biological activities, the pharmacological applications of EOs are limited [235].
due to their insolubility in water, volatility, and instability [220]. Owing Elucidating the role of such drug delivery systems in targeting cancer
to loss of efficiency upon oxidation, exposure to UV/gamma radiations,
28
Table 4
Various drug delivery systems used for targeting essential oils/its constituents for anti-cancerous activity and the possible mechanism involved.
Essential oil source Drug delivery system Targeted cancer cell line (s) and IC50 values Mechanism of action Reference
/ EO component (s)
Carvacrol Nanoemulsions A549, PC-9 human lung adenocarcinoma; Reduced cell viability (= 52.7%) and arrest of [236]
In vitro (At 25–150 µg mL-1 for 24 h): A549, PC-9; cancer cells in sub-G1 phase of cell cycle;
In vivo: Treatment with carvacrol at 50 and induction of apoptosis as a result of activation
100 mg kg-1 body weight of apoptotic proteins such as IRE1-α and p-
JNK, caspases, and cytochrome c, and
decreased expression of p-eIF2α, GRP78, and
CHOP;
In vivo: Decrease in tumour growth and weight
(= 34.2% and 62.1% at 50 and 100 mg kg-1,
respectively)
Citral and related Nanoparticle micelles In vitro: Endometrial cancer (ECC-1), Ovarian cancer Reduction in tumour growth (at 40 and [237]
isomers (geranial (OVCAR-3 and SKOV-3) 80 mg kg-1 body weight) by 60% and 85%,
and neral) In vivo: Mouse breast cancer (4T1) respectively; anti-proliferative activity in all
the cancer cell lines, arrest of cell cycle at G1/S
phase and apoptosis (in ECC-1 and OVCAR-3
cells); increase in autophagy of SKOV-3 and
4T1 cells; increased expression of Bax gene and
activation of p53 (a tumour suppressor)
explains apoptotic activity of citral in ECC-1
and OVCAR-3 cells
Citral Self nano-emulsifying drug Colorectal cancer cells (At 1.56–25 μg mL-1 for 24, Anti-proliferative and cytotoxic activity [152]
delivery system (CIT-SNEDDS) 48, and 72 h): a) HT29: IC50 = 34.10 ± 0.30 μg mL-1
(at 72 h);
b) SW620: IC50 = 16.50 ± 0.87 μg mL-1 (at 72 h)
Citrus bergamia Risso Liposomes SH-SY5Y human neuroblastoma cells (Concentration Improved uptake of the liposomes and cancer [54]
& Poit. used = 0.01–0.05%) cell death
Citrus bergamia Risso Nanoemulsions stabilized by Caco-2 human epithelial colorectal adenocarcinoma Redistribution of protein junction and increase [238]
& Poit. emulsifiers cells (Concentration used = 100 mg L-1) in membrane permeability by emulsifiers for
better EO permeation that further result in
cytoplasmic release
Citrus limon (L.) Nanoemulsions A549 lung cancer cells Induction of apoptosis via increased activation [239]
Osbeck of caspase 3 and suppression of angiogenesis
Cuminum cyminum L. Nanoemulsions SAS tongue carcinoma cells (IC50 = 1.5 µL mL-1) Apoptosis, autophagy, necrosis, and cell cycle [240]
arrest; easy fusion of the nanoemulsions into
the pathogen lipid membranes leading to
membrane disruption, increased leakage of
cytoplasm contents, and cell death
Ferula persica Willd. Gold nanoparticles CT26 murine colon carcinoma cells (IC50 = Decrease in cancer cell viability after 24 h; [241]
0.0024 mg mL-1) induction of apoptosis due to cytochrome c
release, activation of caspases, and increase in
ROS production
Jasminum Nanoencapsulation in pectin/ MCF-7 breast cancer cells (IC50 = 0.0246 mg mL-1) Induction of DNA fragmentation by pectin [242]
grandiflorum L. chitosan nanoparticles leading to cancer cell apoptosis
Linalool Nanoparticles (LIN-NPs) In vitro: Epithelial ovarian carcinoma (HeyA8, Reduction in cell viability; reduction in tumour [243]
A2780, SKOV3ip1); weight [especially by 100 mg kg-1 LIN-NPs (=
In vivo: At 300 and 600 mg kg-1 linalool 58% in HeyA8, 74% in SKOV3ip1); induction
of apoptosis when treated with 2 mmol L-1
LIN-NPs through increased up-regulation of
caspases (3 and 9), and p-ERK
Linalool Nanoparticles (SLN-LN) (At 0.5–2.0 mM linalool for 24 and 48 h): Human Increased cytotoxicity (= 11% and 15% at 1.5 [244]
liver carcinoma (HepG2), Human alveolar and 2.0 mM SLN-LN, respectively in A549 and
adenocarcinoma (A549) 76% growth reduction in HepG2 cells at
2.0 mM for 48 h)
Morinda citrifolia L. Chitosan nanoparticles A549 lung cancer cells (IC50 = 40 µg mL-1) Increased apoptosis; increased ROS levels; [245]
caspase-3 activation, decrease in Bcl-2 protein
levels; loss of mitochondrial membrane
potential; cell cycle arrest in G0/G1 phase
Nigella sativa L. Nanoemulsions MCF-7 breast cancer cells (IC50 = 82 µL mL-1 at 24 h; Easy permeation of EOs into the cell membrane [246]
IC50 = 59 µL mL-1 at 48 h) through increased solubilisation of EO
compounds and induction of apoptosis,
necrosis, and cell death; fragmentation of DNA
and chromatin; reduction/shrinkage of cells
Nigella sativa L. Gold nanoparticles A549 lung cancer cells (IC50 = 28.37 µg mL-1) Reduced cell viability with increasing [247]
concentrations (5–50 µg mL-1); loss of
membrane potential, aggregation of cells
Ocimum gratissimum Chitosan (OGEO-CSNPs) and N, MDA-MB-231 breast cancer cells Decrease in cell viability (= 77.19% and [248]
L. N, N-trimethyl chitosan (OGEO- 37.44% with OGEO-CSNPs and OGEO-
TMCNPs) nanoparticles TMCNPs, respectively); induction of apoptosis
Origanum Nanocapsules and Hep-G2 liver cancer cells; Detoxification of carcinogens via induction of [249]
glandulosum Desf. nanoemulsions Nanocapsules: IC50 = 54.93 µg mL-1; GST
Nanoemulsions: IC50 = 131.6 µg mL-1
Rosmarinus officinalis Nanoliposomes MCF-7 breast cancer cells (cell death = 51%, and Induction of cell toxicity when encapsulated in [250]
L. 58% at 1:3 and 1:4 EO ratio) liposomes
29
Essential oil source Drug delivery system Targeted cancer cell line (s) and IC50 values Mechanism of action Reference
/ EO component (s)
Trachyspermum ammi Poly (lactide-co-glycolide) HT-29 human colon cancer cells (IC50 = Induction of apoptosis, increased expression of [251]
(L.) Sprague nanoparticles 35.94 µg mL-1, 7 µg mL-1, and <7 µg mL-1 for Cas-9/BAX apoptotic genes and decreased
incubation times: 24, 48, and 72 h, respectively) expression of Bcl-2 gene (anti-apoptotic),
suppression of angiogenesis
Trachyspermum Niosomes HepG2 hepatocellular carcinoma cells (IC50 = Cytotoxicity was attributed to the presence of [252]
copticum (L.) Link 180.32 ± 3.6 µg mL-1) EO constituents (i.e. thymol, p-cymene, and
γ-terpinene)
Varthemia iphionoides Silver nanoparticles MDA-MB-231 (breast cancer): IC50 Decrease in cancer cell viability; suppression of [126]
Boiss. & Blanche = 15.8 ± 0.3 µg mL-1, K-562 (chronic myelogenous PI3K/Akt pathway; induction of apoptosis
leukemia): IC50 = 20.2 ± 2.5 µg mL-1, Panc1
(pancreatic cancer): IC50 = 17.4 ± 5.3 µg mL-1, PC-3
(prostate cancer): IC50 = 10.7 ± 0.3 µg mL-1
Zataria sp. Pectin-based nanoemulsions MDA-MB-231: IC50 = 20.4 µg mL-1 (at 72 h), T47D: Induction of apoptosis and cell cycle arrest in [253]
IC50 = 0.0016 µg mL-1 (at 72 h), MCF-7: IC50 G2/M and S phase, increase in intracellular
= 5.38 µg mL-1 (at 72 h) breast cancer cell lines ROS levels, loss of mitochondrial membrane
potential
Abbreviations: IRE1-α: serine/threonine-protein kinase/endoribonuclease inositol-requiring enzyme 1, p-JNK: c-jun N-terminal kinase (phosphorylated form), p-eIF2α:
eukaryotic translation initiation factor 2α, GRP78: glucose regulated protein, CHOP: C/EBP (enhancer binding protein) homologous protein, Bax: Bcl-2-associated X
protein (apoptosis regulator), ROS: reactive oxygen species, ERK: extracellular-signal-regulated kinase, Bcl2: B-cell lymphoma 2, GST: glutathione-S-transferase, PI3K/
Akt: phosphatidylinositol 3 kinase/a serine-threonine specific protein kinase.
Table 5
Various essential oils and their components used in combination with therapeutic drugs for targeting cancer cells and the mechanism of action involved.
Essential oil/its Combination Targeted cancer cell line (s) and IC50 values Mechanism of action Reference
components and delivery drug (s)
system (if any)
Bornyl acetate 5-Fluorouracil SGC-7901 human gastric cancer cells (48 µM bornyl Increase in apoptosis (observable features: chromatin [136]
acetate + 1.5 µM condensation, nuclear fragmentation and shrinkage)
5-fluorouracil) and % of apoptotic cells = 55.9% and arrest of cells in
G2/M phase of cell cycle
Citral Doxorubicin Human Burkitt’s lymphoma (Ramos cells): Doxorubicin Increased cytotoxicity (Combination index = [153]
+ 10/20/40 μM citral: IC50 = 2.16 ± 0.03 μM to 0.99–1.01); induction of apoptosis and cell death with
1.23 ± 0.04 μM doxorubicin + 20/40 μM citral
Citrus limonum Risso Ifosfamide MCF-7 breast cancer cells (Lemon EO + Ifosfamide: IC50 Improved accumulation of combined drug in cancer [254]
(Lemon EO)/ = 0.200 mM; Salvia EO + Ifosfamide: IC50 = cells leading to apoptosis of cancer cells as evinced by
Salvia officinalis L. 0.270 mM) and HeLa cervical cancer cells (Lemon EO + lack of nucleus, formation of cellular vesicles, and
(Salvia EO); Ifosfamide: IC50 = 0.165 mM; Salvia EO + Ifosfamide: autophagocytosis;
Nanoemulsions IC50 = 0.141 mM) Lemon oil: suppression of PI3K/Akt pathway and death
of mitochondria in colon cancer cells;
Salvia oil: suppression of angiogenesis leading to
prevention of tumour growth and invasion
Linalool; Paclitaxel In vivo: Epithelial ovarian carcinoma (HeyA8, A2780, Reduction in mice tumour weight by 80% [243]
Nanoparticles (LIN-NPs) SKOV3ip1) at 50 mg kg-1 LIN-NP + 6 mg kg-1 paclitaxel
Melaleuca alternifolia Dabrafenib/ M14 melanoma cells (50 μg mL-1 at 72 h) Easy permeation into cancer cell membrane via [255]
(Maiden & Betche) Cheel Trametenib inhibition of p170 glycoprotein signalling; Induction of
apoptosis via increment in caspase 3 and cleavage of
PARP; necrosis, cell cycle arrest, anti-invasion of
chemotherapy-resistant cells
Origanum majorana L.; Epirubicin H1299 non-small cell lung cancer line (5–500 μg mL-1 Mitochondrial membrane damage, DNA damage and [256]
Linalool EO/linalool) increase in 8-OHdG levels and cell death; arrest of cell
division; increased cytotoxicity against epirubicin-
resistant cells
Thymoquinone Doxorubicin MCF-7 human breast adenocarcinoma cells (25, 50 or Inhibition of cancer cell growth, induction of DNA [257]
(a component of Nigella 100 μM thymoquinone) fragmentation and apoptosis; increased cleavage of
sativa L. EO) caspases (3, 7, and 9) and PARP; cytochrome C release
from mitochondria; increase in Bax proteins while a
decrease in Bcl levels; arrest of cancer cells in G2/M
phase of cell cycle; activation of PTEN/Akt pathway
Abbreviations: PI3K: Phosphatidylinositol 3 kinase, Akt: a serine-threonine specific protein kinase, PARP: poly-ADP ribose polymerase, OHdG: hydroxydeoxyguanosine,
PTEN: Phosphatase and tensin homolog deleted on chromosome 10, Bax: Bcl-2-associated X protein (apoptosis regulator), Bcl: B-cell lymphoma 2.
cells has lately become the cornerstone of anticancer arsenal (Fig. 5). In changes in expression levels of certain proteins, and modulation in
this direction, recent studies have explored the cytotoxicity of EO lipo signaling pathways [251]. In general, the activation and increased
somes/nanoemulsions/nanoparticles against various types of cancer cleavage of caspases (Cas-3 and Cas-9) and PARP, down-regulation of
(Table 4). For example, nanocapsules of Origanum glandulosum Desf. and Bcl-2 proteins, p-elF2α (eukaryotic initiation factor), GRP78 (gluco
Trachyspermum ammi (L.) Sprague EOs were strongly cytotoxic against se-regulated protein 78), and CHOP (C/EBP homologous protein),
HepG2 liver cancer cell line and colon cancer cell lines (HT-29 and up-regulation of Bax levels, IRE1-α (serine/threonine-protein kin
HUVEC), respectively [249,251]. EOs induce the formation of apoptotic ase/endoribonuclease inositol-requiring enzyme 1 α) and p-JNK (c-Jun
cell bodies through a combination of effects such as DNA damage, N-terminal kinase), release of cytochrome c, and phosphorylation of
30
ERK all contribute to cancer cell apoptosis [236,237,239,241,243,245, CRediT authorship contribution statement
251]. Delivery of bergamot (Citrus bergamia Risso & Poit.) EO liposomes
and nanoemulsions also increased its water solubility and anticancer Harminder Pal Singh, Daizy R. Batish: Project leader, Manuscript
activity in human neuroblastoma and epithelial colorectal adenocarci layout, Manuscript preparation. Kamaljit Grewal, Mansi Sharma: Data
noma cell lines, respectively [54,238]. Cuminum cyminum L. EO nano collection. Mansi Sharma: Data analysis, Manuscript preparation.
emulsions (IC50 = 1.5 µL mL-1) decreased the number of colonies and Rupali Jandrotia: Manuscript preparation. Ravinder Kumar Kohli:
induced apoptosis in tongue cancer cell lines without affecting the Manuscript preparation and editing.
non-cancerous cell lines, thus exhibiting specificity towards cancer cells
[240]. Solubility of jasmine (Jasminum grandiflorum L.) EO was Conflict of interest statement
enhanced when loaded in pectin/chitosan nanoparticles, thereby
increasing its anticancer properties against MCF-7 breast cancer cell line The authors declare that they have no known competing financial
[242]. interests or personal relationships that could have appeared to influence
the work reported in this paper.
3.3.3. Potential applications of EOs in combination with synthetic drugs
Owing to the multitude of benefits explored so far, studying the Data availability
synergistic action of EOs and synthetic drugs in enhancing the anti
cancer potential and minimizing drug-associated side effects is the need No data was used for the research described in the article.
of the hour (Table 5). Use of EOs in synthetic anticancer drug formu
lations can enhance cell death or necrosis of cancer cells by increasing Acknowledgements
cytotoxicity and inhibiting cancer cell invasion by drug-resistant cells
[255,256]. Inhibition of PI3/Akt pathway, suppression of angiogenesis, Mansi Sharma is thankful to University Grants Commission (UGC),
inhibition of p170 glycoprotein signalling, increased activation of cas India for research fellowship. Rupali Jandrotia is thankful to Depart
pases (e.g., caspase-3, caspase-7, and caspase-9), PARP cleavage, cyto ment of Health Research (DHR), India, for research funding.
chrome c release, changes in expression levels of apoptotic proteins
(such as Bax and Bcl-2) are the general protective anticancer mecha
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Biomedicine & Pharmacotherapy 146 (2022) 112514

Contents lists available at ScienceDirect

Biomedicine & Pharmacotherapy

Essential oils as anticancer agents: Potential role in malignancies, drug

apoptosis due to prolonged drug usage, changes in DNA including

1.2. Essential oils: Introduction, nature, and biological activities

The discovery of natural plant-based products is rightly recognized

DANG: IC50 = 1:720;

= 2.5 µg mL-1; A375: IC50 β-ocimene, bornyl acetate,

Human pancreatic apoptotic cells (2.07–68.87% at

100 µg mL-1 EO for 48 h in all the

Human oral Thymus carmanicus Carvacrol, cymene, thymol, borneol,

MDA=MB-231: Curcumin (at 0–80 µM): IC50 2. MDA-MB-231: EC75 concentration

3. Cell growth inhibition and cell cycle

2. Increase in apoptosis genes (such as

closure of wound scratch after 48 h

and increase in activity of caspases and

Table 3 Table 3 (continued )

Table 3 (continued ) Table 3 (continued )

2. Anti-inflammatory, 5. Stimulates nervous

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