Metformin Induces Oxidative Stress-Mediated Apoptosis without the Blockade of Glycolysis in H4IIE Hepatocellular Carcinoma Cells.

Metformin Induces Oxidative Stress-Mediated Apoptosis without the Blockade of Glycolysis in H4IIE Hepatocellular Carcinoma Cells. Biol Pharm Bull. 2019;42(12):2002-2008 Authors: Park D Abstract Metformin, a widely prescribed anti-diabetic drug, also exerts anti-cancer effects in different types of cancers. Although a number of molecular mechanisms have been suggested, the metabolic features underlying metformin's anti-cancer activity is not fully understood enough. Because cancer cells have been known to prefer inefficient aerobic glycolysis to support their proliferation, it is important to clarify by which metformin affects metabolism to suppress the proliferation of cancer cells. Here, we report the metabolic changes induced by metformin and its relevance to the induction of apoptosis in H4II rat hepatocellular carcinoma cells. H4IIE cells were treated with metformin and other reagents in culture media with various nutritional compositions. Glutamine as well as pyruvate enhanced the viability of H4IIE cells in glucose-deprived conditions. Protective effects of glucose and pyruvate were comparable at same concentrations (5 mM). Metformin induced apoptosis irrespective of any nutritional conditions. Glucose consumption and lactate production were stimulated by metformin. Inhibition of glycolysis by 2-deoxyglucose suppressed the metformin-induced lactate production but additively enhanced metformin's pro-apoptotic effect. These res...
Source: Biological and Pharmaceutical Bulletin - Category: Drugs & Pharmacology Authors: Tags: Biol Pharm Bull Source Type: research