Investigation of the apoptotic pathway induced by benzimidazole–oxindole conjugates against human breast cancer cells MCF-7

• Benzimidazole–oxindole conjugates (5c and 5p) showed significant anticancer activity against human breast cancer cell line MCF-7.
• These conjugates were investigated for their apoptotic mechanism against human breast cancer cell line, MCF-7.
• These conjugates induced mitochondrial mediated (intrinsic apoptotic pathway) apoptosis in human breast cancer cell line, MCF-7.
• Moreover, these compounds did not significantly inhibit the noncancerous HEK-293 and Vero cells.

In our previous studies, benzimidazole–oxindole conjugates were synthesized and evaluated by National Cancer Institute (NCI) for their cytotoxic activity and the new molecules like 5c and 5p were considered as potential leads. These conjugates arrested the cell cycle at G2/M phase and inhibited tubulin polymerization. These observations prompted us to investigate the apoptotic mechanism induced by these lead molecules against human breast cancer cells (MCF-7). Studies like measurement of mitochondrial membrane potential (ΔΨm), generation of reactive oxygen species (ROS) and Annexin V-FITC assay revealed that these compounds induced mitochondrial mediated (intrinsic apoptotic pathway) apoptosis in human breast cancer cells. It was further confirmed by western blot analysis of pro apoptotic protein Bax, anti apoptotic protein Bcl-2, cytochrome c release, caspase-9 activity and cleavage of PARP.

Benzimidazole–oxindole conjugates (5c and 5p) were investigated for their apoptotic mechanism against human breast cancer cell line, MCF-7. These conjugates induced mitochondrial mediated (intrinsic apoptotic pathway) apoptosis in human breast cancer cell line, MCF-7.Figure optionsDownload as PowerPoint slide