Effects of Epigallocatechin Gallate on the Cytotoxicity of Epirubicin-HCl in Lung Cancer Cells

Background: Studies have shown that epigallocatechin-3-gallate (EGCG), which is present in green tea at a higher rate than other components, has an additive or synergistic cytotoxic effect when applied with different anticancer drugs and reduces the side effects caused by anticancer drugs. It is known that the order of administration of drugs in combined applications also affects cytotoxicity. In this context, our study determined the most effective application sequence by evaluating the cytotoxic responses of epirubicin-HCl and EGCG according to the different application orders in A-549 cells (NSCLC). Methods: To demonstrate the apoptotic activity, we detected changes in mRNA ratios of Bax, a proapoptotic gene, and Bcl-2, an anti-apoptotic gene (Bax/Bcl2), as well as changes in the activity of caspase 3/7 enzyme. To demonstrate the effect of oxidative stress generation, we investigated changes in glutathione peroxidase activity. Results: It was observed that the cell viability of A-549 cells exposed to different concentrations of epirubicin- HCl and EGCG for 48 h decreased depending on the concentration increase. According to the results of cell viability in cells to which epirubicin-HCl (< IC50) and EGCG (< IC50) were treated together, and the combination index (CI) value calculations, the most effective combination concentrations were determined to be IC20 Epirubicin-HCl and IC10 EGCG. LDH activities were higher in epirubicin-HCl + EGCG treatment than in the epirubicin-HCl alone treatment compared to control groups. Treatment of epirubicin-HCl with EGCG was found to be more effective in increasing glutathione peroxidase activity than epirubicin-HCl alone. Both epirubicin-HCl alone and combination treatments caused an increase in Bax/Bcl-2 ratio in A-549 cells. Conclusion: Combination therapy of epirubicin-HCl with EGCG may be helpful in the future for lung cancer patients trying to be treated with conventional chemotherapy drugs but cannot achieve the desired success.