ABSTRACT
The biguanide drug metformin used for treating Type 2 diabetes has anticancer properties and affects many pathways involving glucose metabolism, energy balance, and cell survival. A number of retrospective clinical studies have indicated a reduced risk of cancer and improved cancer outcomes in Type 2 diabetic patients taking metformin. Several of its effects are mediated through the induction of cellular stress and subsequent activation of AMP kinase, but many other mechanisms act independently of AMP kinase activation. Metformin has been shown to inhibit the effects of tumor necrosis factor (TNF)-alpha. TNF-alpha interferes with insulin signaling to produce insulin resistance in the insulin signaling pathway and promotes apoptosis through NF-KB in the apoptosis pathway. In addition, metformin reduces cellular proliferation by decreasing the amount of available insulin or by directly affecting the mammalian target of rapamycin complex involved with regulating protein synthesis. It can prevent tumors from acquiring stem cell-like properties, upregulate apoptotic pathways, and bolster the immune system's fight against cancer. Gaining a greater understanding of metformin's various mechanisms of action will continue to elucidate metformin's role as an effective treatment for cancer.
