Pomegranate fruit juice for chemoprevention and chemotherapy of prostate cancer

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. Pomeg...

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Bibliographic Details
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
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0505870102