Genistein Enhances TRAIL-Mediated Apoptosis Through the Inhibition of XIAP and DcR1 in Colon Carcinoma Cells Treated with 5-Fluorouracil

Abstract

Objectives: Colorectal cancer is one of the most common cancers in the world. However, surgical intervention and chemotherapy provide only limited benefits for the recovery and survival of patients. The anti-carcinogenic effect of genistein has attracted attention due to epidemiological studies showing that soybean consumption is associated with a decrease in incidence of cancer. There are limited studies on the effects of genistein in colorectal carcinoma cells. We aimed to investigate the cytotoxic, genotoxic, and apoptotic effects of genistein in SW480 and SW620 colon adenocarcinoma cells treated with 5-fluorouracil, the basis of chemotherapy, and TRAIL ligand, the mediator of apoptosis, both alone and in combination. Materials and Methods: The cytotoxicity and genotoxicity were determined by MTT assay and comet assay, respectively. The apoptotic effects were evaluated by RT-PCR assay, with the additional use of Annexin V FITC, mitochondrial membrane potential, caspase 3, 8 and 9 activity, reactive oxygen species assay kits. Results: According to our findings, genistein, 5-fluorouracil and TRAIL had synergistic apoptotic effects as a result of DR5 up-regulation, ROS production, and DNA damage, which was mediated by increased caspase 3, 8 and 9 activity and decreased mitochondrial membrane potential. Conclusion: The applied combinations of these compounds may contribute to the resistance problem that may occur in the treatment of colorectal cancer, with the decrease in DcR1 and XIAP genes.