Brusatol inhibits growth and induces apoptosis in pancreatic cancer cells via JNK - p38 MAPK - NF-κb - Stat3 - Bcl-2 signaling pathway - Request PDF

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Brusatol inhibits growth and induces apoptosis in pancreatic cancer cells via JNK/p38 MAPK/NF-κb/Stat3/Bcl-2 signaling
pathway
April 2017 · Biochemical and Biophysical Research Communications 487(4)

DOI:10.1016/j.bbrc.2017.04.133
Authors:
Yukai Xiang Wen Chaohao Huang Bin

Wenzhou Medical University Ye California State University, Chico Lou
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Citations (68) References (38)
Abstract
Brusatol, isolated from brucea, has been proved to exhibit anticancer

Discover the world's
influence on various kind of human malignancies. However, the role
research
that brusatol plays in pancreatic cancer is seldom known by the public.
Through researches brusatol was proved to inhibit growth and induce 25+ million
apoptosis in both PATU-8988 and PANC-1 cells by decreasing the
members
expression level of Bcl-2 and increasing the expression levels of Bax,
Cleaved Caspase-3. Then we found the activation of the JNK, p38 160+ million
MAPK and inactivation of the NF-κb, Stat3 are related with the potential publication
pro-apoptotic signaling pathways. However, SP600125 could not only pages
abrogated the JNK activation caused by brusatol, but also reverse the 2.3+ billion
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p38 activation and the decrease of Bcl-2 as SB203580 did. Besides, citations
SP600125 and SB203580 also reversed the inactivation of NF-κb and
Stat3. Furthermore, BAY 11–7082 and S3I-201 indeed had the similar
effect as brusatol had on the expression of Phospho-Stat3 and Bcl-2.
To sum up, we came to a conclusion that in pancreatic cancer, brusatol
do inhibit growth and induce apoptosis. And we inferred that brusatol
illustrates anticancer attribution via JNK/p38 MAPK/NF-κb/Stat3/Bcl-2
signaling pathway.
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Citations (68) References (38)
https://www.researchgate.net/publication/316465447_Brusatol_inhibits_growth_and_induces_apoptosis_in_pancreatic_cancer_cells_via_JNKp… 1/13
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Zhang et al. have found citation
that MCF-7 Copy
human breast cancer cellslink
lose their MMP after
treatment with 5 μM brusatol, thus causing apoptosis, as also confirmed in Bel-7402
human liver cancer [28]. Other studies have concluded that brusatol causes a substantial
imbalance between Bcl-2 and Bax [21,39,50,60,62, 64, 67]. The increasing Bax/Bcl-2 ratio
results in the disengagement of Cyt C together with other related proteins, thus promoting
the caspase cascade and apoptosis. ...
... Pancreatic cancer, because of its poor prognosis in both men and women, ranked
seventh in terms of cancer-associated mortality in 2020, with approximately 496,000 cases
and 466,000 deaths worldwide [114]. Brusatol inhibits growth and induces apoptosis in
pancreatic cancer cells via suppression of the JNK/p38 MAPK/ NF-κB/Stat3/Bcl-2 pathway
[64] . Brusatol enhances the chemotherapeutic effect of gemcitabine in pancreatic cancer
by inhibiting the Nrf2 signaling pathway and increasing ROS accumulation in vitro and in
vivo [62]. ...
... Cuendeta et al. have demonstrated that brusatol induces differentiation of the HL-60 cell
line via NF-κB activation, through a process involving p50 and p65, which is inhibited by
SN50, an NF-κB translocation inhibitor [47]. Xiang et al. have demonstrated that brusatol
induces apoptosis and inhibits growth by inhibiting the NF-κB signaling pathway in both the
PANC-1 and PATU-8988 cell lines, whereas these effects are attenuated by the MAPK
inhibitors SP600125 and SB203580 [64] . ...
Brusatol modulates diverse cancer hallmarks and signaling pathways as a potential

cancer therapeutic
Article Full-text available
Jul 2022
Song-Bin Guo · Wei-Juan Huang · Xiao-Peng Tian
View Show abstract
... They also reported that BT suppressed c-Myc expression and overexpression of c-Myc
blocked brusatol-driven HIF-1α degradation [30]. In another report, BT was found to
activate JNK and p38 MAPK pathways with concurrent inhibition of proinflammatory
signaling pathways such as NF-κB and STAT3 in pancreatic cancer cells [31] . In the
present investigation, we tested the effect of BT on the constitutive STAT3 signaling
cascade in HNSCC cell lines. ...
... BT has been reported to exhibit prominent anticancer activity in several preclinical
cancer models. BT can induce its anticancer effects via modulating multiple cellular
signaling events such as Nrf-2, HIF-1α, c-Myc, JNK/p38 MAPK/NF-κB/Stat3/Bcl-2
signaling pathways [31] . Xiang et al. showed that BT can downregulate the
phosphorylation of STAT3 in pancreatic cancer cells but the detailed mechanism of
inhibition was not deciphered [31]. ...
... BT can induce its anticancer effects via modulating multiple cellular signaling events
such as Nrf-2, HIF-1α, c-Myc, JNK/p38 MAPK/NF-κB/Stat3/Bcl-2 signaling pathways [31].
Xiang et al. showed that BT can downregulate the phosphorylation of STAT3 in pancreatic
cancer cells but the detailed mechanism of inhibition was not deciphered [31] . The cousin
compound of BT called bruceantin has also gained significant attention due to its potent
antitumor activity in mouse models. ...
Brusatol, a Nrf2 Inhibitor Targets STAT3 Signaling Cascade in Head and Neck Squamous
Cell Carcinoma

Sep 2019
Jong Hyun Lee · Shobith Rangappa · Mohan Chakrabhavi Dhananjaya · Kwang Seok Ahn
View Show abstract
... Ren and coworkers in 2011 described for the first time how Nrf2-mediated mechanism
of defense is suppressed by BR [88]. An in vitro study on pancreatic cell lines PATU-8988
and Panc1 further indicated that BR monotherapy resulted in substantial cytotoxicity in
these cells [89] . Furthermore, the follow-up investigation showed an enhanced
therapeutic effect of gemcitabine in combinatorial treatment with BR, evidenced by
increased apoptosis and diminished xenograft formation [90]. ...
... Furthermore, the follow-up investigation showed an enhanced therapeutic effect of
gemcitabine in combinatorial treatment with BR, evidenced by increased apoptosis and
diminished xenograft formation [90]. Xiang et al. showed that BR inhibits growth and
induces apoptosis in pancreatic cancer cells-PATU-8988 and Panc1, through the activation
of the JNK (c-Jun N-terminal Kinase)/p38 MAPK (mitogen-activated protein kinase) and
subsequent inhibition of NF-κB/STAT3/BCL2 signaling [89] . These observations were
further confirmed in 2018 by the same group as BR reduced the Nrf2 protein content in a
Keap1-independent manner and decreased the expression of genes related to the multiple
drug resistance (MDR) family involved in gemcitabine resistance of pancreatic cancers
[90]. ...
Role of Nrf2 in Pancreatic Cancer

Dec 2021
Marta Cykowiak · Violetta Krajka-Kuźniak
View Show abstract
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... Previous studies showed that several quassinoids of Fructus Bruceae possessed
significant anticancer activity against pancreatic cancer cell lines (PANC-1, SW1990,
CAPAN-1) [10][11] [12] , such as brusatol, bruceine D, and bruceine H. Among them,
brusatol exhibited the most potent in vitro antipancreatic cancer cation, with half-maximal
inhibitory concentration (IC 50 ) values of 0.36 lM and 0.10 lM on PANC-1 and SW1990
cell lines, respectively [11]. ...
... Recent years, brusatol potentiated gemcitabine-induced apoptosis and growth inhibition
in pancreatic cancer cells, which has been widely explored [11,26]. Notably, brusatol
induced apoptosis by activating p38a MAPK pathways in PANC-1 and PATU-8988 cell
lines [12] . Here, our fortebio octet system assay identified bruceine A could directly bind to
p38a MAPK with higher affinity than brusatol. ...
A Novel P38α MAPK Activator Bruceine A Exhibits Potent Anti-Pancreatic Cancer Activity
Jun 2021
Cai Lu · Lu Fan · Peng-Fei Zhang · Ming Zhao
View Show abstract
... C-Jun N-terminal kinase (JNK) is one of the most important pathways in the mitogen-
activated protein kinase (MAPK) family that is mainly involved in stress response and
apoptosis, among other physiological processes (5). The accumulation of reactive oxygen
species (ROS) induces apoptotic signal transduction and activates apoptotic proteins, such
as caspase-3 and Bax, causing apoptosis (6, 7). The bodily production of ROS is induced
through the action of various factors causing oxidative stress, leading to activation of
apoptosis signal-regulating kinase 1 (ASK1). ...
... The bodily production of ROS is induced through the action of various factors causing
oxidative stress, leading to activation of apoptosis signal-regulating kinase 1 (ASK1). In
turn, JNK phosphorylation is promoted, and phosphorylated JNK further activate and
promote the overexpression of the apoptosis proteins Bax, cysteinyl aspartate-speci c
proteinase-3 (caspase-3), resulting in liver cell apoptosis, which can lead to liver
degeneration and necrosis ( Fig. 1) (6, 8,9). ...
Role and Mechanisms of Probiotics in Regulating the ROS/JNK Signaling Pathway in the
Pathogenesis of Nonalcoholic Fatty Liver Disease.
Preprint Full-text available
Jan 2021
Huiyuan Xu · LeiLei Yang · Yumei Huang · Changping Li
View Show abstract
... nuclear factor (nF)-κB p65 and is an important transcription factor that regulates of
inflammatory genes including TNFα, il-1β, IL-6, IL-10, IL-12, and cyclooxygenase-2 [10,11].
Also, nF-κB increases B-cell lymphoma 2 (Bcl-2) expression, resulting in a decrease in
cellular apoptosis [12] [13][14]. ...
... The effects on weight gain correlated well with the changes in colon length and colon
mass index. The DSS induced decrease in colon length may be related to the submucosal
edema shown histologically while the colon shortening may be associated with its
thickening due to edema and infiltration of inflammatory cells into the lamina propria and
submucosa [12, 14]. RENE led to marked reduction in the inflammatory infiltrate in both
lamina propria and submucosa and dose-dependently protected against changes in colon
length. ...
Resveratrol Nanoemulsion; A Promising regulator of TGFB1and TFF-3 Genes Expression

in DSS-Induced Ulcerative Colitis in Rats
Jan 2021
Mohammed Abdalla Hussein · Mohamed Samieh Nasr Eldin Aboshanab
View
... The role of the nuclear factor kappa B (NF-κB) pathway in the regulation of cancer cell
apoptosis has been extensively studied, and it has been shown to protect cancer cells
against apoptosis (Bours et al. 2000). Some studies have indicated that MAPK and AKT
can induce cancer cell apoptosis via the phosphorylation and activation of the STAT3 and
NF-κB pathways (Ke et al. 2017; Xiang et al. 2017 ). In addition, the transduction and
execution of apoptotic signal require the coordinated effect of cysteine aspartase
(caspase) cascade. ...
... Apoptosis was analyzed using the Apoptosis and Necrosis Assay Kit and the Annexin V
Apoptosis Detection Kit (Xiang et al. 2017) . Briefly, the HepG2 and Hep3B cells were
seeded into 6-well plates (1 × 10 5 cells/well/2 ml) for 24 h. ...
Liquiritin inhibits proliferation and induces apoptosis in HepG2 hepatocellular carcinoma
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via the ROS-mediated Download citation
MAPK/AKT/NF-κB Copy link
signaling pathway
Oct 2020 · N Schmied Arch Pharmacol

Jia-Ru Wang · Tian-Zhu Li · Cheng Wang · Cheng-Hao Jin
View Show abstract
... The Annexin V-FITC/PI Apoptosis Detection Kit (Solarbio) was used to examine cell
apoptosis [47] . In 6 well plates, human GC MKN-45 cells (1 × 10 5 cells/well) were grown
and exposed to 87 µM C3G for 3, 6, 12, and 24 h. ...
Cyanidin-3-O-Glucoside Induces the Apoptosis of Human Gastric Cancer MKN-45 Cells

through ROS-Mediated Signaling Pathways
Jan 2023 · MOLECULES

Wei Sun · Nai-Dan Zhang · Tong Zhang · Cheng-Hao Jin
View Show abstract
... It has been reported that HOXA10 can activate ERK and p38 signaling pathways,
thereby regulating cell proliferation and apoptosis [10]. Abnormal activation of ERK and
p38 signaling pathway is related to the occurrence and development of EC; even more,
activation of P38 and ERK pathway can promote the progression of EC [11] [12] [13].
However, whether HOXA10 can participate in the progression of EC by regulating p38 and
ERK pathways needs further study. ...
HOXA10 enhances cell proliferation and suppresses apoptosis in esophageal cancer via
activating p38/ERK signaling pathway
Nov 2022
Lifeng Jiang · Qixian Yang
View Show abstract
... MDA, a marker of oxidative damage, can cause an abnormal physiological state in the
body [23]. GSH, an active peptide with good antioxidant activity, can modulate oxidative
balance and suppress oxidative damage [24] . In this study, we investigated the
cytoprotective effects of phenolic acids on H 2 O 2 -induced oxidative stress in EA.hy 926
endothelial cells. ...
Comparison of the Antihypertensive Activity of Phenolic Acids

Sep 2022 · MOLECULES
Myeongnam Yu · Hyun Joo Kim · Huijin Heo · Junsoo Lee
View Show abstract
... Brusatol (Bru; Figure 1) is a quassinoid plant extract isolated from the Brucea species
plant, capable of inducing various biological effects, including antimalarial, anti-
inflammatory, and antineoplastic. Its potential as an antineoplastic drug was reported in
several solid tumors, such as pancreatic cancer (PC), non-small cell lung cancer (NSCLC),
renal cell cancer (RCC), among others [9] [10] [11][12][13][14][15][16][17], as well as in
hematological malignancies and particularly acute myeloid leukemia (AML) [18]. Previous
investigations demonstrated that brusatol could act as a global protein synthesis inhibitor
[19], while most studies reported it as an inhibitor of NRF2 signaling by reducing its protein
levels through post-transcriptional mechanisms stimulating its ubiquitination and
subsequent proteolysis [20,21]. ...
Antitumor Effect of Brusatol in Acute Lymphoblastic Leukemia Models Is Triggered by

Reactive Oxygen Species Accumulation
Sep 2022
Joana Jorge · Nisa Magalhães · Raquel Alves · Ana Bela Sarmento-Ribeiro
View Show abstract
... Subsequent studies have found that BRU causes rapid and even instantaneous
depletion of Nrf2 protein through the posttranscriptional mechanism, thus playing a
significant inhibitory effect on the proliferation of HCC cells [18]. At present, it has been
Request pointed
full-text out that brusatol,Download citation
the traditional Chinese medicine, Copy link
has inhibitory effects on a
variety of tumors like liver cancer [19], pancreatic cancer [20] , nasopharyngeal carcinoma
[21], and melanoma [22]. However, there are few reports about brusatol on colorectal
cancer, and its mechanism of action has not been clearly described. ...
Brusatol Inhibits Proliferation and Metastasis of Colorectal Cancer by Targeting and

Reversing the RhoA/ROCK1 Pathway
May 2022 · BMRI
Rui-Jin Lu · Guo-zhi Zhao · Rong Jiang · Jing Li
View Show abstract
... The Wnt pathway is involved in the stress fiber alignment process but not their
formation. Along with its reported role in stress fiber alignment 63 , JNK is also involved in
the p38-MAPK pathway 67, 68 , which is known to have comprehensive cross-talk with the
Wnt pathway 46 . Inhibition of the Wnt pathway alone with tankyrase resulted in similar
outcomes which suggest the involvement of the Wnt/p38-MAPK pathway in the fiber
alignment process. ...
Statistical parametrization of cell cytoskeleton reveals lung cancer cytoskeletal phenotype

with partial EMT signature
May 2022
Arkaprabha Basu · Manash K Paul · Mitchel Alioscha-Perez · Shimon Weiss
View Show abstract
... Nuclear factorkappa B (NF-κB) is a crucial regulator in the malignant transformation and
survival of leukemia cells [21,22]. In addition, accumulating evidence indicates that the
mutual crosstalk exists between MAPK and NF-κB signaling pathways [23][24] [25] , the
most important one of which is mediated by the Gadd45 family of proteins. Gadd45
proteins are a group of critical signal sensor involved in the regulation of multiple cell
functions by connecting upstream receptor module transcription NF-κB and transcription
regulation module MAPK. ...
Hinokiflavone induces apoptosis, cell cycle arrest and autophagy in chronic myeloid
leukemia cells through MAPK/NF-κB signaling pathway
Apr 2022
Xiang Qin · Xi Chen · Ling Guo · Wenzhe Ma
View Show abstract
... Bru was further demonstrated to function as a protein synthesis inhibitor but not a
specific Nrf2 inhibitor, thus, Bru is able to rapidly reduce the levels of short-lived proteins
[21]. In addition, Bru has also been demonstrated to inhibit epithelial-mesenchymal
transition (EMT), tumorigenesis and metastasis via regulating multiple signaling pathways,
including c-Myc, mitogen-activated protein kinase (MAPK), janus kinase 2 (JAK2)/signal
transducer and activator of transcription 3 (STAT3), and phosphatidylinositol-3-kinase
(PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathways [22] [23]
[24][25]. However, the direct targets of Bru remain unknown. ...
Brusatol has therapeutic efficacy in non-small cell lung cancer by targeting Skp1 to inhibit
cancer growth and metastasis
Article
Jan 2022 · PHARMACOL RES
Shangping Xing · Feifei Nong · Yaqin Wang · Yong-Qiang Liu
View Show abstract
... The Nrf2 inhibitory action of BT is correlated with its capacity to suppress tumorigenicity
and tumor cell migration and invasion [111]. For instance, in PATU-8988 and PANC-1
pancreatic cancer cells, it mediated apoptosis by inactivating NF-κB/signal transducer and
activator of transcription 3 (STAT3) and activating JNK/p38 MAPK signaling [112] . As a
potential inhibitor of Nrf2 and STAT3, BT actively suppressed tumor formation and
progression in head and neck squamous cell carcinoma, as well [113]. ...
Cancer Chemopreventive Role of Dietary Terpenoids by Modulating Keap1-Nrf2-ARE

Signaling System-A Comprehensive Update
Nov 2021
Md Afjalus Siraj · Md. Arman Islam · Md. Abdullah Al Fahad · Jesus Simal-Gandara
View Show abstract
... Our results add SAE to the list of diseases in which p38MAPK drives pathophysiology
and may therefore be a useful therapeutic target. Analogously, inhibiting p38MAPK using
SB203580 has been shown in vitro to reverse the dysregulation of NF-κB and downstream
STAT3 and to slow pancreatic tumor growth [47] . Therefore, as shown in Fig. 11, knocking
out or downregulating CXCR5 reduces p38MAPK activation and, consequently, its
downstream signaling, ultimately ameliorating sepsis-induced cognitive defects. ...
CXCR5 down-regulation alleviates cognitive dysfunction in a mouse model of sepsis-

associated encephalopathy: potential role of microglial autophagy and the p38MAPK/NF…
Oct 2021 · J NEUROINFLAMM
Yanan Shen · Yuan Zhang · Jiayue Du · Yanna Si
View Show abstract
... The Wnt pathway is involved in the stress fiber alignment process but not their
formation. JNK is also involved in the p38-MAPK pathway 60, 61 , which is known to have
comprehensive cross-talk with the Wnt pathway 46 . Inhibition of the Wnt pathway alone
with tankyrase resulted in similar outcomes which suggests the involvement of the p38-
MAPK pathway in the fiber alignment process. ...
Image quantification technique reveals novel lung cancer cytoskeletal phenotype with
partial EMT signature
Preprint
Jun 2021
Arkaprabha Basu · Manash K Paul · Mitchel Alioscha-Perez · Shimon Weiss
View Show abstract
... Our results add SAE to the list of diseases in which p38MAPK drives pathophysiology
and may therefore be a useful therapeutic target. Analogously, inhibiting p38MAPK using
SB203580 has been shown in vitro to reverse the dysregulation of NF-κB and downstream
STAT3 and to slow pancreatic tumor growth [47] . We show here that knocking out or
down-regulating CXCR5 reduces p38MAPK activation and, consequently, its downstream
signaling, ultimately ameliorating sepsis-induced cognitive defects. ...
CXCR5 Down-regulation Alleviates Cognitive Dysfunction in a Mouse Model of Sepsis-

associated Encephalopathy: Potential Role of Neuronal Autophagy and the p38MAPK/NF…
May 2021
Yanan Shen · Yuan Zhang · Jiayue Du · Yanna Si
View Show abstract
... It sensitizes multiple types of cancer cells to anti-cancer drugs by downregulating Nrf2
expression via ubiquitination-dependent degradation 22 . Many studies showed that the
inhibitory activity of brusatol is not restricted to Nrf2 ; it can also rapidly and potently
decrease the expression of sevral other proteins including HIF-1α, p38, STAT3 and
SQSTM1 [23] [24] [25] , which implies that brusatol is a global protein synthesis inhibitor
26-28 . Despite ubiquitination-dependent degradation is an important manner for brusatol
to suppress protein expression, increasing evidence illustrates brusatol can also regulate
its targets at the transcriptional level. ...
Brusatol Sensitizes Endometrial Hyperplasia and Cancer to Progestin by Suppressing

Nrf2-Tet1-AKR1C1-Mediated Progestin Metabolism
Apr 2021
Meiyan Hu · Di Sun · Jing Yu · Zhenbo Zhang
View Show abstract
... Brusatol is known as an inhibitor of Nrf2 in increasing oxidative damage and triggering
cancer lethality [76]. This phytochemical can induce apoptosis in cancer cells via down-
regulating anti-apoptotic factor Bcl-2 and stimulating JNK/p38 axis [77] . By down-
regulating c-Myc as a tumor-promoting factor, brusatol increases hypoxia inducible factor-
1α (HIF-1α) degradation and suppresses cancer progression under hypoxic conditions
Request [78].
full-text
... Download citation Copy link
Nrf2 signaling pathway in cisplatin chemotherapy: Potential involvement in organ

protection and chemoresistance
Article
Mar 2021
Sepideh Mirzaei · Aliasghar Tabatabaei Mohammadi · Mohammad Hossein Gholami ·
Masoud Najafi
View Show abstract
... BRU is an inhibitor of nuclear factor erythroid derivative 2 (Nrf2) (12) and its positive
effects have been reported in various cancers such as pancreas and lung cancers (13,14).
It has also been found to be effective in various intracellular signaling pathways (11, 15) . ...
Nrf2 Inhibitor Brusatol Ameliorates Cecal Ligation and Puncture-induced Lung Injury in
Rats via Anti-inflammation and Anti-oxidative Stress
Jan 2020
Ersen Eraslan · Ayhan Tanyeli · Mustafa Can Guler · Elif Polat
View
... 240 Furthermore, brusatol inhibited the cell growth of PaTu 8988 and Panc-1 human
pancreatic cancer cells and induced apoptosis in these cells through the JNK (c-Jun N-
terminal kinase)/p38 MAPK (mitogen-activated protein kinase)/NF-κB/STAT3/Bcl2
signaling pathway. 241 A further nonesterified analogue of BRC, bruceine D (9j), also has
attracted interest for its antitumor potential. It was found to inhibit human breast and lung
cancer cell growth and suppressed the viability, metastasis, and EMT of MDA-MB-231
human breast cancer cells. ...
Development of Potential Antitumor Agents from the Scaffolds of Plant-Derived Terpenoid

Lactones
Dec 2020
Yulin Ren · A. Douglas Kinghorn
View Show abstract
... Oxidative stress is closely related to cell apoptosis, which is mainly related to the
mitochondrial pathway, the mitogen activated protein kinase (MAPK) pathway,
endoplasmic reticulum stress, NF-κB, and Bcl-2 family [31] . In the Bcl-2 family, there are
inhibitory factors, such as Bcl-2, and pro-apoptotic factors, such as Bax, and both of them
have a synergistic effect. ...
The effect of Malus doumeri leaf flavonoids on oxidative stress injury induced by
hydrogen peroxide (H2O2) in human embryonic kidney 293 T cells
Sep 2020
Yanyan Li · Yunyi Li · Zhie Fang · Junda Wang
View Show abstract
... In addition, the ROS-mediated signal transducer and activator of transcription 3 (STAT3)
and nuclear factor-κB (NF-κB) pathways play an important role in cancer progression (10)
(11)(12)(13). Increasing evidence has suggested that ROS induce cell apoptosis by
activating the MAPK, STAT3 and NF-κB signaling pathways in cancer cells (14, 15) . ...
Isoorientin induces the apoptosis and cell cycle arrest of A549 human lung cancer cells
via the ROS‑regulated MAPK, STAT3 and NF‑κB signaling pathways
Article
Jun 2020
Wan-Ting Xu · Gui-Nan Shen · Tian-Zhu Li · Cheng-Hao Jin
View Show abstract
... Brusatol increases hypoxia-inducible factor-1 (HIF-1) alpha degradation and induces cell
death by inhibiting the c-Myc/ROS signaling pathway in colorectal cancer under hypoxia
[14]. In addition, brusatol inhibits growth and induces apoptosis in pancreatic cancer cells
via the JNK/p38 MAPK/NF-kappa B/Stat3/Bc1-2 signaling pathway [38] . Moreover,
Request brusatol
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of chemotherapy Copy
by inhibiting link
Nrf2-mediated defense in a
broad range of cancer cells [17,22,23]. ...
Anticancer effects of brusatol in nasopharyngeal carcinoma through suppression of the

Akt/mTOR signaling pathway
Jun 2020 · CANCER CHEMOTH PHARM
Song-Bin Guo · Jinling Zhang · Cairong Wei · Zhenfeng Zhang
View Show abstract
... C-Jun N-terminal kinase (JNK) is a member of the mitogen-activated protein kinase
superfamily. The JNK signaling pathway can be activated by cytokines, growth factors,
stress, and other factors, and is involved in various physiological processes such as cell
proliferation and differentiation, cell apoptosis, and stress response [18, 19]. In addition,
JNK signaling pathway is closely related to the activation of autophagy and plays an
important role in the occurrence and development of neurodegenerative diseases,
ischemia reperfusion injury, and other diseases [20]. ...
Role of JNK Signaling Pathway in Dexmedetomidine Post-Conditioning-Induced Reduction

of the Inflammatory Response and Autophagy Effect of Focal Cerebral Ischemia…
Dec 2019 · INFLAMMATION
Yulin Zhu · Shihong Li · Jingying Liu · Kun Xie
View Show abstract
... NRF2targeting agents can be used to overcome antioxidant response-dependent

chemotherapeutic-resistance [24] and brusatol, a quassinoid extracted from Brucea
javanica, has been shown to enhance the efficacy of chemotherapy by inhibiting the
NRF2-mediated defense mechanism [25,26]. Brusatol may abrogate gemcitabine-induced
NRF2 activation in pancreatic cancer cells to restore chemosensitivity of cancer cells [48];
may enhance the radiosensitivity of lung cancer cells by promoting ROS production and
enhancing DNA damage [49]; and may inhibit cancer cell growth and induce apoptosis via
JNK/ p38 MAPK/NF-κb/Stat3/Bcl-2 [50] . In line with these findings, we show that brusatol
re-sensitized cancer cells to drug cytotoxic activity inhibited by HG and inhibited NRF2-
dependent activity. ...
Reduced chemotherapeutic sensitivity in high glucose condition: implication of

antioxidant response
Jul 2019
Alessia Garufi · Gianandrea Traversi · Maria Saveria Gilardini Montani · Gabriella D'Orazi
View Show abstract
... For example, promoting p38/JNK pathway prevented colorectal cancer development by
suppressing EMT [42]. In pancreatic cancer cells, the activity of p38/JNK signaling
elevated apoptosis to inhibit the pancreatic cancer progression [43] . Moreover, studies
have shown that the signaling kinase ERK, a key regulator in cancer progression, plays
critical roles in the process of tumor metastasis in a variety of cancer types [39,44,45]. ...
Decrease of MLK4 prevents hepatocellular carcinoma (HCC) through reducing metastasis

and inducing apoptosis regulated by ROS/MAPKs signaling
Aug 2019 · BIOMED PHARMACOTHER
Yu Li · Haibo Zuo · Hongjian Wang · Anxiang Hu
View Show abstract
Unlocking the Potential of Brusatol as an Antitumoral Agent: Molecular Mechanisms and

Therapeutic Benefits
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Parameswary V Marar · Ayush Kumar · Rajan Swami · Manish Kumar Jeengar
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Terpenoids A Potential Scaffold for Cancer Therapy: A Mechanistic Approach

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Oct 2023
Surya Kant Tripathi · Stuti Biswal · Munmun Panda · Bijesh Kumar Biswal
View Show abstract
Brusatol induces ferroptosis in oesophageal squamous cell carcinoma by repressing GSH

synthesis and increasing the labile iron pool via inhibition of the NRF2 pathway
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Xu Zhu · Nannan Huang · Yao Ji · Junting Ma
View
Implications of NRF2 in Cancer Progression and Therapeutics

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Sep 2022
Madhunika Agrawal · Dr. Satyam Kumar Agrawal
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Culture media from hypoxia conditioned mast cells aggravates hypoxia and reoxygenation
injury of human intestinal cells
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Brusatol: A potential sensitizing agent for cancer therapy from Brucea javanica
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Ting He · Fangli Zhou · Anping Su · Wenshuang Wu
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Induction of apoptosis by ethanolic extract of leaf of Dillenia pentagyna in A549 cells via
NF-κB pathway
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Targeting tumor glycolysis metabolism in oral squamous cell carcinoma cells by brusatol
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Guilian Zhang · Yanlin Wu · Suhong Chen · Xinyan Zhang
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Role of caspase-3-cleaved/activated PAK2 in brusatol-triggered apoptosis of human lung

cancer A549 cells
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Chien-Hsun Huang · Fu Ting Wang · Wen-Hsiung Chan
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Brusatol sensitizes endometrial hyperplasia and cancer to progestin by suppressing

NRF2-TET1-AKR1C1-mediated progestin metabolism
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THE MOLECULAR APPROACH OF NATURAL PRODUCTS AS PANCREATIC CANCER

TREATMENT: A REVIEW
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Muhammad Fauzan Lubis · Poppy Anjelisa Zaitun Hasibuan · Urip Harahap · Ririn Astyka
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12/22/23, 12:14 PM Brusatol inhibits growth and induces apoptosis in pancreatic cancer cells via JNK/p38 MAPK/NF-κb/Stat3/Bcl-2 signaling p…

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Citations (68) References (38)

Brusatol, isolated from brucea, has been proved to exhibit anticancer

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Citations (68) References (38)

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