Metforminin Sitotoksik, Apoptotik ve Genotoksik Etkilerinin İn Vitro Değerlendirilmesi.

Abstract

Metformin is a biguanide derivative widely used in the treatment of diabetes mellitus. Recent studies have shown the anticancer properties of metformin. The possible mechanisms of anticancer effects of metformin have not been fully elucidated. For this reason, interest in the effects on cell proliferation and apoptosis has increased in various human cancer cell lines and studies have been started. In this thesis, it is aimed to investigate cytotoxic, genotoxic and apoptotic effects of metformin on HepG2 and HeLa cell lines. Metformin in HepG2 cells did not produce a significant cytotoxic effect when compared to (-) control after 48 h incubation in the 0.5 - 2 mM concentration range; but at a concentration of 4 mM and above, there was a statistically significant decrease in cell viability in a dose-dependent manner. The IC50 value in the HepG2 cells was found to be 57.3 mM. In HeLa cells, metformin did not produce a significant cytotoxic effect when compared to (-) control after 48 h incubation in the concentration range of 0.5-16 mM; but cell viability decreased in a dose-dependent manner at concentrations of 32 and 64 mM which was statistically significant. The IC50 value in HeLa cells was found to be 76.9 mM. It was determined that when compared to (+) control all the concentrations of metformin (5-1000 μM) in the HepG2 and HeLa cells were statistically significantly reduced by the Comet method. Cell cycle analysis with HepG2 cells revealed a 10 % apoptosis in the cell population at a concentration of only 32 mM. Effect of metformin on cell cycle in HepG2 cells, increase in G0 / G1 phase accumulation was observed at 4, 8 and 64 mM concentrations compared to (-) control (80 %) and it was found higher compared with the (-) control of cell cycle (91 %, 99 %, 97 % respectively). Proliferation was observed in HepG2 cells. Cell cycle analysis with HeLa cells revealed apoptosis of 30 %, 39 %, 27 % in the cell population at 4, 32 and 64 mM concentrations, respectively. Our results have shown that it may reduce oxidative DNA damage in non-cytotoxic high doses of metformin and may lead to apoptosis, but further studies are needed to support these results.