APOPTOSIS AND GENOTOXICITY ASSESSMENT INDUCED BY

ORGANOTIN(IV) N-METHYL-N-BENZYL DITHIOCARBAMATE

COMPOUNDS AGAINST HUMAN LUNG CARCINOMA CELL LINES
(A549)
ABD AZIZ, N.A.1, AWANG, N. 1*, CHE ENGKU SHOPIAN, C.E.K. 2, KAMALUDIN, N.F. 1

1
Center for Toxicology and Health Risk Studies, Faculty of Health Sciences, Universiti
Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia.
2
Environmental Health and Industrial Safety Program, Faculty of Health Sciences, Universiti
Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia.
norm@edu.ukm.my

Cisplatin, a frequently utilized cancer treatment, is notorious for its notable adverse effects on
patients. Recently, there has been an increasing interest in organotin(IV) compounds as potential
agents for combating cancer due to their heightened efficacy, decreased toxicity, and improved
elimination from the body. This study aims to explore the cell death mechanism and genetic
damage caused by two specific compounds, namely dibutyltin(IV) N-methyl-N-benzyl
dithiocarbamate (referred to as Compound 1) and triphenyltin(IV) N-methyl-N-benzyl
dithiocarbamate (referred to as Compound 2), in A549 cells. The methodology involved
maintaining human lung cancer cells (A549) in a specified medium under controlled conditions.
Subsequently, the cells were subjected to doses corresponding to their respective IC50 values, and
the mechanism of cell death induced by these compounds was evaluated using an Annexin V-
FITC/PI assay to discern between apoptosis and necrosis. Additionally, the genotoxicity induced
by Compound 2 was scrutinized using an alkaline comet assay. The results demonstrated that both
compounds induce apoptotic cell death in A549 cells, with Compound 1 showing a higher
apoptotic cell death rate (62.3%) compared to Compound 2 (58.27%). Furthermore, Compound 2
was observed to induce DNA damage within a mere 30 minutes of treatment. In summary, this
investigation suggests that organotin(IV) dithiocarbamate compounds exert potent cytotoxic
effects on A549 cells, prompting further exploration into their mechanisms of action. These
findings underscore the potential of these compounds as a promising new class of anticancer
therapeutics.