Journal
PHARMACEUTICAL RESEARCH
Volume 27, Issue 6, Pages 1128-1137Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11095-010-0052-7
Keywords
apoptosis; cell cycle arrest; prostate cancer; white cocoa
Funding
- Chinese Government
- United States Public Health Service [RO1 CA 78809, RO1 CA 101039, RO1 CA 120451, P50 DK065303]
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We evaluated the chemotherapeutic effect of water extract of white cocoa tea (WCTE) against human prostate cancer (PCa) in vitro and in vivo. Cell viability and cell cycle distribution were determined by MTT assay and flow cytometry, respectively. Western blotting was performed to determine changes in levels of various proteins. Effect of WCTE was determined in athymic nude mice implanted with PC-3 cells. Treatment with WCTE (100-150 A mu g/ml) inhibited cell proliferation, which correlated with G2/M phase arrest in PC-3 cells. WCTE treatment to PC-3 cells resulted in (1) induction of WAF1/p21 and KIP1/p27, (2) decrease in cyclins D1, D2 and E, (3) decrease in cyclin-dependent kinase (cdk) 2, 4 and 6, (4) induction of Bax and down-regulation of Bcl-2, (5) decrease in procaspase-3, -8, (6) inhibition of nuclear translocation and phosphorylation of NF-kappa B and activation of IKK alpha, and (7) inhibition of phosphorylation and degradation of I kappa B alpha. Oral administration of WCTE (0.1 and 0.2%, wt/vol) to athymic nude mice resulted in greater than 50% inhibition of tumor growth. There was a decrease in expressions of cyclin D1, Bcl-2 and p-NF-kappa B and an increase in WAF1/p21 and Bax in tumor tissues of mice. WCTE can be a useful chemotherapeutic agent against human PCa.
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