New perspectives for metformin in cancer therapy
Abstract
Cancer and type II diabetes are two diseases that appear to be associated. In fact, diabetes increases the incidence of several cancers (colon, endometrium, rectum and breast). Retrospective epidemiological studies show that metformin, a drug commonly used in type II diabetes, has antitumor properties. Therefore, many experimental studies (in vivo and in vitro) have been initiated in recent years to understand the cellular and molecular mechanisms that may explain the protective effects of metformin against cancer. Two main mode of action have been proposed. The first, indirect, involves the decrease of insulinemia. The second, via a direct action on cells, results in the regulation of the activated AMPK kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway, which plays a central role in many cellular processes such as energy metabolism, protein synthesis, autophagy and apoptosis. Here, we review recent results concerning the antitumor action of metformin: epidemiological, metabolic, cellular and molecular levels. Ongoing experimental and clinical trials should help us better understand the mechanisms of action of metformin and allow us to determine whether the drug can be used in the treatment of cancer.
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