Polyphenols Isolated from Propolis Augment TRAIL-Induced Apoptosis in Cancer Cells

Epidemiological data support the concept that phenols and polyphenols in diet are safe and nontoxic, and have long-lasting beneficial effects on human health. The potential target for complementary and alternative medicine (CAM) research has been on the discovery of natural compounds that can be used in the prevention and treatment of cancer. Propolis is one of the richest sources of plant phenolics (flavonoids and phenolic acids). The ethanolic extract of propolis (EEP) and its polyphenols possess immunomodulatory, chemopreventive, and antitumor effects. Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) is a  naturally occurring anticancer agent that preferentially induces apoptosis in cancer cells and is not toxic to normal cells. Endogenous TRAIL plays a significant role in immunosurveillance and defense against cancer cells. However, as more tumor cells are reported to be resistant to TRAIL-mediated death, it is important to develop new strategies to overcome this resistance. EEP and polyphenols isolated from propolis have been shown to sensitize cancer cells to TRAIL-induced apoptosis. In this paper we demonstrate for the first time the crucial role of the main phenolics isolated from propolis in enhancing TRAIL-mediated death in tumor cells for cancer chemoprevention.