Metformin, cancer and glucose metabolism.

Metformin is the first-line treatment for type 2 Diabetes. Several clinical studies have reported that type 2 diabetic Patients treated with metformin might have a lower cancer risk. One of the primary metabolic changes observed in malignant cell transformation is an increased catabolic glucose metabolism. In this context, once entered into the cell through organic cation transporters (OCT), metformin decreases mitochondrial respiration chain activity and ATP production that, in turns, activates AMP-activated protein kinase (AMPK), which regulate energy homeostasis. In addition, metformin reduces cellular energy availability and glucose entrapment by inhibiting hexokinase-II, which catalyses the glucose phosphorylation reaction. In this review, we will discuss recent findings on metformin molecular mechanisms that sustain its anti-cancer effect through regulation of glucose metabolism. In particular, we will focus on the emerging action of metformin on glycolysis in normal and cancer cells with a drug discover