Pomegranate-derived constituents as inducers of cell death: Implications in cancer prevention and therapy

Abstract

Cancer chemoprevention, the process of administrating agents which inhibit, delay or reverse the process of carcinogenesis, represents one of the most novel and promising approaches in cancer research. Significant epidemiological evidence suggests an association between increased consumption of fruits, vegetables and spices with a reduced risk of cancer. Bioactive components present in fruits and vegetables, especially polyphenolic flavonoids such as anthocyanins and catechins, show antioxidant, anti-inflammatory and pro-apoptotic effects which afford chemopreventive properties. Pomegranate, obtained from the tree Punica granatum has been suggested as an excellent chemopreventive dietary agent. The pomegranate tree, especially the fruit has been a part of medical and religious folklore for centuries. Pomegranates are an extremely rich source of several complex polyphenolic flavonoids such as anthocyanins, hydrolyzable tannins such as punicalin and ellagic acid as well as fatty acids such as punicic acid. Pomegranate phytochemicals have been shown to demonstrate potent anti-tumor promoting effects due to its antioxidant, anti-inflammatory and apoptosis-inducing properties. Apoptosis, programmed cell death, is one of the most important cancer arresting mechanisms and an important target for chemopreventive strategy. Several studies provide evidence highlighting the pro-apoptotic effects of both the polyphenolic and non-polyphenolic bioactive components of pomegranate. This chapter reviews, in detail, the pro-apoptotic and anti-tumor effects of pomegranate-derived constituents in both in vivo as well as in vitro studies in pre-clinical models of breast, colon, hematological, skin and prostate cancer. The role of synergy, highlighting the importance of poly-constituent pomegranate extracts, bioavailability studies as well as the critical need for clinical studies are discussed.