In vitro assessment of cytotoxic, apoptotic and genotoxic effects of metformin

Abstract

Background and Aims: Recent studies have shown the anticancer properties of metformin, which is widely used in diabetes mellitus. The possible mechanisms of anticancer effects of metformin have not been fully elucidated. We aimed to investigate thecytotoxic, genotoxic, and apoptotic effects of metformin in HepG2 and HeLa cells.Methods: The cytotoxicity, genotoxicity, and apoptotoic effects were determined by MTT method, Comet assay, and FACSassay, respectively.Results: Metformin significantly decreased cell viability above 4 and 32 mM in HepG2 and HeLa cells, respectively, for 48 h.The IC50 values were 57.3 mM (HepG2) and 76.9 mM (HeLa). Metformin (5-1000 µM) alone did not increase DNA damage inall cells. It did not change oxidative DNA damage in HepG2 cells but induced oxidative DNA damage in HeLa cells. HepG2cells treated with only 32 mM metformin revealed 10% apoptosis. G0/G1 phase accumulation was statistically higher in thecells treated with 4, 8, and 64 mM metformin (91%, 99%, and 97% respectively) than in (-) control (80%). HeLa cells revealedapoptosis of 30%, 39%, 27% at 4, 32, and 64 mM concentrations, respectively. The results implicate that the inhibition ofHepG2 cell viability may be due to the arrest of cell cycle in G0/G1 phase and apoptosis, whereas apoptotic response is mainlyresponsible for the cytotoxicity of metformin in HeLa cells.Conclusion: Metformin may not induce DNA damage at non-cytotoxic high doses and lead to apoptosis, even if compatiblewith previous data. This study provides important information that metformin may play an essential role in apoptosis andcell cycle progression in carcinoma cell lines, which can explain the anticancer effects of metformin, but further studies areneeded to support these results.