Pomegranate fruit juice for chemoprevention and chemotherapy of prostate cancer

<jats:p> Prostate cancer is the most common invasive malignancy and the second leading cause of cancer-related deaths among U.S. males, with a similar trend in many Western countries. One approach to control this malignancy is its prevention through the use of agents present in diet consumed by humans. Pomegranate from the tree <jats:italic>Punica granatum</jats:italic> possesses strong antioxidant and antiinflammatory properties. We recently showed that pomegranate fruit extract (PFE) possesses remarkable antitumor-promoting effects in mouse skin. In this study, employing human prostate cancer cells, we evaluated the antiproliferative and proapoptotic properties of PFE. PFE (10-100 μg/ml; 48 h) treatment of highly aggressive human prostate cancer PC3 cells resulted in a dose-dependent inhibition of cell growth/cell viability and induction of apoptosis. Immunoblot analysis revealed that PFE treatment of PC3 cells resulted in ( <jats:italic>i</jats:italic> ) induction of Bax and Bak (proapoptotic); ( <jats:italic>ii</jats:italic> ) down-regulation of Bcl-X <jats:sub>L</jats:sub> and Bcl-2 (antiapoptotic); ( <jats:italic>iii</jats:italic> ) induction of WAF1/p21 and KIP1/p27; ( <jats:italic>iv</jats:italic> ) a decrease in cyclins D1, D2, and E; and ( <jats:italic>v</jats:italic> ) a decrease in cyclin-dependent kinase (cdk) 2, cdk4, and cdk6 expression. These data establish the involvement of the cyclin kinase inhibitor-cyclin-cdk network during the antiproliferative effects of PFE. Oral administration of PFE (0.1% and 0.2%, wt/vol) to athymic nude mice implanted with androgen-sensitive CWR22Rν1 cells resulted in a significant inhibition in tumor growth concomitant with a significant decrease in serum prostate-specific antigen levels. We suggest that pomegranate juice may have cancer-chemopreventive as well as cancer-chemotherapeutic effects against prostate cancer in humans. </jats:p>