In Vitro Anticancer Effects of Stilbene Derivatives: Mechanistic Studies on HeLa and MCF-7 Cells

Abstract

Background and Objective: The growing prevalence of cancer and the resulting chemoresistance exert not only a great healthcare burden but is also a great challenge to public health, worldwide. In search of new chemical entities against cancer, triazine hybrids of stilbene scaffold were investigated for their anticancer potential. Materials and Methods: Synthetic triazine hybrids of stilbene were used for determination of their anticancer potential for cervical (HeLa) and breast (MCF-7) carcinoma cells. Hit compound (7e) namely, sodium (E)-6,6'-(ethene-1,2-diyl)bis(3- ((4-chloro-6-((3-luorophenyl)amino)-1,3,5-triazin-2-yl)amino)benzenesulfonate) was explored further for mechanistic studies. Results: In a set comprised of twelve derivatives, compound, sodium (E)-6,6'-(ethene-1,2-diyl)bis(3-((4-chloro-6-((3- luorophenyl)amino)-1,3,5-triazin-2-yl)amino)benzenesulfonate) (7e) was found most active against HeLa and MCF-7 cells. The present study has revealed that compound 7e may activate mitochondrial pathway of apoptosis in HeLa and MCF-7 cells which was assessed by DNA binding studies, estimation of release of Lactate Dehydrogenase (LDH), fluorescence imaging, production of Reactive Oxygen Species (ROS) in cancer cells, analysis of cell cycle by flow cytometry, change in Mitochondrial Membrane Potential (MMP) and activation of caspase-9 and caspase-3, respectively. Conclusion: Compound 7e may serve as a lead in designing new anticancer compounds from stilbene scaffold.