Chemoprevention of Prostate Cancer by Allspice Derived Polyphenol: Ericifolin

The aromatic berries of the Jamaican plant Pimenta dioica (Allspice) are used in many cuisines for their delectable flavor and as folk remedies for a variety of ailments. Despite being as a rich source of antioxidants the use of Allspice as cancer preventive or anticancer agent needs to be investigated. The overall goal of this proposal is to investigate the potential use of Aqueous All spice Extract (AAE) against prostate cancer. Potential anti-cancer activity of an Aqueous All spice Extract (ME) will be tested on prostate cancer (CaP) cells and tumor models. It was already found in preliminary studies that AAE inhibited tumor cell proliferation (lC5o-~10Oug/ml), clonogenic growth (1C50-4Oug/ml), and invasive potential (40%) of various CaP cells tested. AAE was selectively toxic to tumor cells and less toxic to non-tumorigenic cells. The goal of this proposal is to explore how AAE blocks the cell cycle progression, and which signal transduction pathways are involved. Our hypothesis is that AAE affects the G1 phase, inhibits G1 to S phase transition by decreases cyclin Dl. Phosphorylation of Rb and CDK4 and P21 levels might also be affected. ME-induced apoptosis is believed to be specific to androgen responsive, androgen receptor expressing (ARt) cells where, and ME treatment may induce depolarization of mitochondria and generation of excessive hydroxyl-free radicals. Preliminary resulys showed that ME-treated cells exhibited increased caspase activity, cleaved-PARP levels, BAX and a decrease in anti- apoptotic proteins like BID. Further analysis of ME is necessary, particularly the isolation and identification of the active principles, using bioactivity-guided fractionation.