The Role of Dietary Polyphenols in Tumor Necrosis Factor-related Apoptosis Inducing Ligand (TRAIL)-induced Apoptosis for Cancer Chemoprevention

Polyphenols, occurring in vegetables, fruits, herbs, spices, propolis, tea, beer, and wine play an important role in cancer chemoprevention. Dietary polyphenols exert their chemopreventive effect by multiple molecular mechanisms of action on apoptosis signaling pathways in cancer cells. In this review, we describe dietary polyphenols targeting the tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-mediated apoptotic pathway. TRAIL is a natural potent anticancer agent that preferentially induces apoptosis in cancer cells and is not toxic to normal cells. Soluble or expressed on immune cells, molecules of TRAIL take part in immune surveillance and defense mechanisms against tumor cells. However, some cancer cells are resistant to TRAIL-mediated cytotoxicity. The decreased expression of death receptors (TRAIL-R1, TRAIL-R2) and proapoptotic proteins or increased expression of antiapoptotic proteins in cancer cells is involved in TRAIL resistance. There is a growing body of experimental evidence showing that polyphenols sensitize TRAIL-resistant cancer cells and markedly augment TRAIL-induced programmed death in cancer cells. These in-vitro and in-vivo studies indicate the significance of dietary polyphenols in cancer chemoprevention strategies through enhancing the apoptosis-inducing potential of TRAIL.