Synergistic effect of resveratrol in combination withcisplatin against oxidative damage and oxidative stressindex on MCF-7 cells

Cancer is the most common cause of death after cardiovascular diseases. Breast cancer is an important health problem with the reason that it is the most common type of cancer in women. Cisplatin (CDDP) is a widely used chemotherapeutic agent against lung, cervix, breast, testicle and brain cancers. Cisplatin's anticancer activity comes from its ability to induce DNA damage and oxidative stress in cells. Resveratrol (RSV) is a potent antioxidant flavonoid belonging to stilbenoids. It has been shown that RSV has many biological activities including anti-cancer, estrogenic/ anti-estrogenic, anti-inflammatory, anti-coagulant and cardioprotective activity. Within the scope of this thesis study, apoptotic and oxidative stress inducing effects of CDDP and RSV combinations against MCF-7 breast adenocarcinoma cells was investigated. MTT assay was used to determine the cytotoxic effects of CDDP and RSV. IC50 values of CDDP and RSV was found at 96±12 μM and 180±16 μM respectively. KM30 (28,8 μM CDDP + 54 μM RSV) and KM40 (38,4 μM CDDP + 72 μM RSV) combinations were prepared from percentages of IC50 doses. To evaluate the apoptotic effects of CDDP, RSV and combinations; Annexin V-FITC/PI, MMP and TUNEL assays were conducted. In all of the experiments that were conducted to detect apoptosis, KM40 combination caused the highest apoptotic response. In order to determine the compounds effect on cells oxidative balance, Total Antioxidant Status (TAS) and Total Oxidant Status (TOS) colorimetric assays were used and by using the data from these assays, Oxidative Stress Index (OSI) was calculated. When compared to the cisplatin-only group (OSI: 1,97), combinations (KM30: 0.70, KM40: 1,60) reduced the oxidative stress of cells. In conclusion, combinations of low doses of CDDP and RSV, synergistically inhibited the growth of MCF-7 cells by inducing apoptosis and reduced the oxidative stress caused by CDDP.