Abstract
Background: 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.
Method: 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.
Results: 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.
Conclusion: Although the results of recent trials confirm the efficacy of metformin in prevention and treatment of different cancers, the evidences are not adequate enough.
Keywords: Metformin, adenosine monophosphate (AMP)-activated protein kinase (AMPK), insulin-like growth factor 1 (IGF-1), kappalight- chain-enhancer of activated B cells (NF-κB), type 2 diabetes mellitus, reactive oxygen species.
Graphical Abstract
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