Abstract
Metformin is widely used for 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. This paper reviews recent available evidences for anti-cancer 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. Adenosine Monophosphate (AMP)-Activated Protein Kinase (AMPK) plays an important role in 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 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 prevention and treatment of different cancers, the evidences are not adequate enough.
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