Basic Science Dietary flavones enhance the effect of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on bladder cancer cells

Abstract

Introduction. Flavonoids, naturally occurring in fruits and vegetables, demonstrate cancer chemopreventive properties. Flavones, a subclass of flavonoids, promote growth inhibition and apoptosis in bladder cancer cells. TRAIL plays an important role in immune surveillance and the defense mechanism against tumor cells. However, not all tumor cells are sensitive to TRAIL. TRAIL-resistant cancer cells can be sensitized to TRAILinduced apoptosis by anticancer agents. We investigated the effect of TRAIL in combination with dietary flavones on bladder cancer cells. Materials and methods. Two human bladder transitional cancer cell (TCC) lines: SW780 and RT112 were incubated with TRAIL and/or flavones (flavone, chrysin, apigenin, luteolin). Cytotoxicity was determined by MTT and LDH assays. results. Our study confirmed that RT112 bladder cancer cells were resistant to TRAIL, whereas SW780 cells were sensitive to TRAIL. We therefore examined the cytotoxic effect of TRAIL in combination with flavones on bladder cancer cells. We showed for the first time that flavones markedly augmented TRAIL mediated cytotoxicity against TCC cells. The strongest cytotoxic effect in combination with TRAIL was exhibited by luteolin. Co-treatment of bladder cancer cells with TRAIL and dietary flavones, especially luteolin, significantly sensitized bladder cancer cells to TRAIL induced cytotoxicity. Conclusion. The tested flavones enhance the cytotoxic effect of TRAIL on bladder cancer cells. The obtained results suggest that dietary flavones (in particular luteolin) supported TRAIL-induced cytotoxicity in TCC cells and thus they might be promising chemopreventive agents in bladder cancer.