Genistein enhances TRAIL-mediated apoptosis through the inhibition of XIAP and DcR1 in colon carcinoma cells treated with 5-fluorouracil

INTRODUCTION: Objectives: Colorectal cancer is one of the most common cancers in the world. How-ever, surgical intervention and chemotherapy provide only limited benefits for the re-covery and survival of patients. The anti-carcinogenic effect of genistein has attracted attention due to epidemiological studies showing that soybean consumption is associ-ated 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, geno-toxic, 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.
METHODS: 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 po-tential, caspase 3, 8 and 9 activity, reactive oxygen species assay kits.
RESULTS: 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 dam-age, which was mediated by increased caspase 3, 8 and 9 activity and decreased mitochondrial membrane potential.

DISCUSSION AND CONCLUSION: 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.