woensdag 5 juni 2013

Allspice extract (Pimenta dioica) and ericofolin against prostate cancer.

Ericifolin: a novel antitumor compound from allspice that silences androgen receptor in prostate cancer
Nagarajarao Shamaladevi1,2, Dominic A. Lyn1, Khaled A. Shaaban3, Lei Zhang1, Susana Villate1, Jürgen Rohr3 and Bal L. Lokeshwar1,2,4,5,* Department of Urology (M-800), School of Medicine, University of Miami, PO Box 016960, Miami, FL 33101, USA. Accepted April 3, 2013.

Silencing of androgen receptor (AR) signaling is a specific and effective mechanism to cure cancer of the prostate (CaP). In this study, the isolation and characterization of a compound from the aromatic berries of Pimenta dioica (allspice) that silences AR is presented. Potential antitumor activities of an aqueous allspice extract (AAE) and a compound purified from the extract were tested on CaP cells. AAE inhibited tumor cell proliferation and colony formation (50% growth inhibition∼40–85 µg/ml) but not the viability of quiescent normal fibroblasts or non-tumorigenic prostate cells. In tumor cells, AAE inhibited cell cycle progression at G1/S, induced apoptosis or autophagy. Apoptosis was by caspase-dependent poly (ADP ribose) polymerase cleavage. A caspase-independent, apoptosis-inducing factor-mediated mechanism of apoptosis caused cell death in castration-resistant AR-positive or AR-negative CaP cells, such as CWR22RV1, PC-3 or DU145 cells. Treatment with AAE decreased the levels of AR messenger RNA (mRNA), protein and silenced AR activity in AR-positive cells. AR depletion was due to inhibition of AR promoter activity and mRNA stability. Delayed tumor growth (~55%) without measurable systemic toxicity was observed in LNCaP tumor-bearing mice treated with AAE by oral or intraperitoneal routes. LNCaP tumor tissues from AAE-treated mice revealed increased apoptosis as a potential mechanism of antitumor activity of AAE. The chemical identity of bioactive compound in AAE was established through multistep high-performance liquid chromatography fractionation, mass and Nuclear Magnetic Resonance spectroscopies. The compound, eugenol 5-O-β-(6′-galloylglucopyranoside) or ericifolin (EF), showed antiproliferative, pro-apoptosis and anti-AR transcription activities. These results demonstrate a potential use of AAE and EF against prostate cancer.

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