Metformin and Its Implication in Cancer Therapy

Abstract

Metformin has been used for almost half a century as the first line of treatment for type 2 diabetes. Mechanisms of action are still incompletely known, recent studies have shown that metformin exerts its effects through several mechanisms, including the stimulation of AMP-activated protein kinase, decreasing production of cyclic AMP, inhibition of mitochondrial complex I of the electron transport chain, targeting glycerophosphate dehydrogenase and altering gut microbiota. In recent years, studies have shown that patients with type 2 diabetes mellitus have a lower risk of developing cancer, and patients with cancer and type 2 diabetes have a lower mortality. Experimental studies have demonstrated that metformin has anti-tumor activity by inhibiting mTORC1 signaling pathway and mitochondrial complex, inhibiting tumor growth and proliferation, and inducing cellular apoptosis. There are multiple studies showing that combination of metformin with different types of anti-cancer therapies may reduce toxicities and tumor resistance. This chapter is focused on the progress made in understanding the anti-tumor effect of metformin and its association with cancer therapy