Abstract
Metformin is the most common biguanide used in the treatment of diabetes, with 120 million treated patients worldwide. Metformin decreases hyperglycemia without inducing hypoglycemia in diabetic patients and is very well tolerated. The principal effects of metformin are to decrease hepatic gluconeogenesis and increase glucose absorption by skeletal muscles. These effects are primarily due to metformin's action on mitochondria, which requires the activation of metabolic checkpoint AMP-activated protein kinase (AMPK). AMPK is implicated in several pathways, and following metformin activation, it decreases protein synthesis and cell proliferation. Many studies have examined the role of metformin in the regulation of cancer cells, particularly its effects on cancer cell proliferation and cell death. Encouraging results have been obtained in different types of cancers, including prostate, breast, lung, and skin cancers (melanoma). Furthermore, many retrospective epidemiological studies in diabetes patients have shown that metformin treatment decreased the risk of cancers compared with other antidiabetic treatments. In this review, we will discuss the effects of metformin on melanoma cells. Together, our novel data demonstrate the importance of developing metformin and new biguanide-derived compounds as potential treatments against a number of different cancers, particularly melanoma.