Pomegranate fruit juice for chemoprevention and chemotherapy of prostate cancer

• Published in: Proceedings of the National Academy of Sciences - PNAS 2005-10, Vol.102 (41), p.14813-14818
• Main Authors: Malik, A, Afaq, F, Sarfaraz, S, Adhami, V.M, Syed, D.N, Mukhtar, H
• Format: Article
• Language: English
• Subjects: Animals; anticarcinogenic activity; Antioxidants; Apoptosis; Apoptosis - drug effects; Biological Sciences; Cell cycle; Cell growth; Cell Line, Tumor; cell lines; cell proliferation; Cell Survival - drug effects; chemoprevention; Chemotherapy; cyclin-dependent kinase; Cyclins; Dose-Response Relationship, Drug; enzyme inhibitors; Enzyme-Linked Immunosorbent Assay; Fruit juices; Fruits; Gene Expression Regulation, Neoplastic - drug effects; Humans; Immunoblotting; Juices; Lythraceae - chemistry; Male; Mice; Mice, Nude; Microscopy, Fluorescence; neoplasm antigens; oral administration; Phytotherapy - methods; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; pomegranates; Prostate cancer; prostatic neoplasms; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - prevention & control; Protein synthesis; Punica granatum; Time Factors; Tumor burden; Tumors
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0505870102

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 Punica granatum 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 microgram/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 (i) induction of Bax and Bak (proapoptotic); (ii) down-regulation of Bcl-X(L) and Bcl-2 (antiapoptotic); (iii) induction of WAF1/p21 and KIP1/p27; (iv) a decrease in cyclins D1, D2, and E; and (v) 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 CWR22R1 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.