Isoflavones augment the effect of tumor necrosis factor-related apoptosis-inducing ligand (TRA IL) on prostate cancer cells

Introduction. Isoflavones are the subclass of flavonoids with chemopreventive and anticancer activities. Isoflavones induce cytotoxicity and apoptosis in prostate 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 flavonoids. We investigated the effect of TRAIL in combination with isoflavones on prostate cancer cells. Materials and methods. The LNCaP human prostate cancer cells were incubated with TRAIL and/or isoflavones (daidzein, puerarin, ipriflavone, genistein, neobavaisoflavone, and biochanin-A). Cytotoxicity was determined by MTT and LDH assays. Results. Our study confirmed that LNCaP prostate cancer cells were resistant to TRAIL. We therefore examined the cytotoxic effect of TRAIL in combination with isoflavones on LNCaP cells. We showed for the first time that tested isoflavones markedly augmented TRAIL mediated cytotoxicity against prostate cancer cells. The strongest cytotoxic effect in combination with TRAIL was exhibited by neobavaisoflavone and biochanin-A. Co-treatment of prostate cancer cells with TRAIL and isoflavones, especially neobavaisoflavone and biochanin-A significantly sensitized LNCaP cells to TRAIL induced cytotoxicity. Conclusion. The tested isoflavones augmented the cytotoxic effect of TRAIL on LNCaP cells. The obtained results suggest that isoflavones supported TRAIL-induced cytotoxicity in prostate cancer cells and thus they might be a promising chemopreventive strategy in prostate cancer.