Evaluation of The Effects of Genistein on DNA Damage by single cell gel electrophoresis (COMET) in colon cancer cells

Nowadays, it is known that cancer causes more deaths than heart diseases and colorectal cancer is one of the most common cancers. However, surgical intervention and chemotherapy provide limited benefit in the recovery and survival of patients. The most important factors in not seeing the expected treatment efficacy are the drug resistance that develops in patients and the need for targeted treatment that can reduce side effects and allow patient compliance. In order to contribute to the studies conducted to increase the efficacy of colorectal cancer treatment, in this project it was investigated that the exposure cytotoxic effects of SW480 and SW620 colon adenocarcinoma cells to genistein with known anticancer effects, 5-fluorouracil, which is the basis of chemotherapy, and TRAIL ligand, which is the mediator of apoptosis, were investigated by MTT method, genotoxic effects were investigated by Comet method, reactive oxygen species, mitochondrial membrane potential, caspase 3-8-9 activities with the help of kits, apoptotic effects were investigated by flow cytometry and RT – PCR method. It has been determined that genistein, 5-fluorouracil and TRAIL have cytotoxic effects and increase DNA damage in SW480 and SW620 cells. It has been observed that these substances have synergistic apoptotic effects in combination, and that an increase in reactive oxygen species, an increase in caspase 3-8-9 levels and a decrease in mitochondrial membrane potential may be effective in apoptosis induction. In addition, TRAIL was found to induce DR5-mediated apoptosis in cells. In the double and triple combinations in our study, although it was significant in SW480 cells, there was a decrease in DcR1 and XIAP antiapoptic gene expressions in both cell lines compared to the group in which TRAIL ligand was applied alone, and it is thought that this effect may contribute to the elimination of TRAIL resistance.