Abstract
Breast cancer is the fifth leading cause of death, worldwide affecting both genders. Accumulating evidence suggests that metformin, an oral hypoglycemic agent used in the management of type 2 diabetes, exerts anti-tumor effects in many cancers, including the breast cancer. Resveratrol, a natural product found abundantly in many fruits, exhibits marked cytotoxic and pro-oxidant effects. This study was designed to investigate the effect of metformin in combination with resveratrol and cisplatin in MCF-7 cells. Study groups were as follows: untreated control group, single treatment groups (metformin, resveratrol, and cisplatin), double treatment groups (metformin + resveratrol, metformin + cisplatin, and cisplatin + resveratrol) and triple treatment groups (metformin + resveratrol + cisplatin). Our results indicated that metformin inhibits proliferation of MCF-7 cells, an effect that was associated with ROS production and G0/G1 cell cycle arrest, but not apoptosis. Moreover, resveratrol suppressed the proliferation of MCF-7 cells by induction of apoptosis as well as cell cycle arrest. Notably, a significant inhibitory effect in the co-treatment of metformin, resveratrol, and cisplatin was observed which was attributed to induction of autophagy-mediated cell death and apoptosis along cell cycle arrest. In conclusion, our results advocate the anti-cancer properties of metformin and resveratrol on MCF-7 cell s via induction of cell cycle arrest. Additionally, synergistic anti-cancer effects of metformin in a triple combination with cisplatin and resveratrol was attributed to induction of autophagy-mediated cell death and apoptosis along cell cycle arrest. Based on our findings it is proposed that patients may benefit from addition of a drug with a safe profile to conventional anticancer therapies.
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