TRAIL (Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand) mediated Apoptosis of human breast cancer cells sensitized by dietary flavonoid Kaempferol

Abstract

Kaempferol is one of the most prevailing flavonoid distributed in edible plants while TRAIL(tumor necrosis factor-related apoptosis-inducing ligand)is a promising anti-cancer agent. Resistance to TRAIL, limits its potential as a drug for cancer therapy. Cytotoxicity induced by Kaempferol and TRAIL alone and in combination was measured by MTT assay. Apoptosis was detected by DNA fragmentation assay and measured by real time PCR and western blotting techniques. The study clearly showed the dose dependent cytotoxic effect of Kaempferol in combination with TRAIL in all the breast cancer cells. The dying cells showed characteristics of apoptosis such as DNA fragmentation in combined treatment with Kaempferol and TRAIL in human breast cancer cells appreciably, compared to single treatments. Furthermore, it has also been found that treatment with Kaempferol enhances TRAIL-induced apoptosis by increasing expression of apoptosis-related proteins including caspase-3, 8, 9 and Bax and by decreasing the expression of Bcl-2. The present work for the first time shows that the combined treatment with Kaempferol and TRAIL drastically induced apoptosis in human breast cancer cells as compared to single treatment. Thus, the data clearly demonstrates that Kaempferol sensitizes human breast cancer cells to TRAIL-mediated apoptosis, which could have potential therapeutic significance in treating breast cancer.