Anti-cancer Effects of Metformin: Recent Evidences for its Role in Prevention and Treatment of Cancer

Metformin is widely used for the management of type 2 diabetes mellitus (T2DM). Recently growing evidences have shown its anti-cancer effects. The results are mainly from observational studies and thus few information is available concerning the mechanisms of action. Adenosine Monophosphate (AMP)-Activated Protein Kinase (AMPK) plays an important role in the mechanism of action of metformin. The anti-cancer mechanisms of metformin include direct and indirect effects. The direct effects of metformin include AMPK-independent and AMPK-dependent effects whereas the decrease in glucose level, hyperinsulinemia, and Insulin-like Growth Factor 1 (IGF-1) level are considered its indirect effects. Metformin also decreases both pro-inflammatory cytokines and Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) and improves the immune response to cancer cells. Although the results of recent trials confirm the efficacy of metformin in the prevention and treatment of different cancers, the evidences are not adequate enough. This paper reviews recently available evidences for anticancer effects of metformin. The effects of metformin in specific cancers including colorectal, prostate, pancreatic, renal, cervical, endometrial, gastric, lung, breast, and ovarian cancer are reviewed.