Inhibition of CWR22Rnu1 tumor growth and PSA secretion in athymic nude mice by green and black teas.
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AuthorsSiddiqui, Imtiaz A.
Aziz, Moammir H.
Reagan-Shaw, Shannon R.
Adhami, Vaqar M.
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AbstractCancer of the prostate gland (CaP), the most common invasive malignancy and a major cause of cancer related deaths in male population in the USA, is an ideal candidate disease for chemoprevention because it is typically detected in elderly population with a relatively slower rate of growth and progression. Many dietary phytochemicals are showing promising chemopreventive effects, at-least in pre-clinical models of CaP. Our published data in cell culture and animal studies, supported by the work from other laboratories, as well as epidemiological observations and case-control studies, suggest that polyphenols present in green tea possess CaP chemopreventive and possibly therapeutic effects. This present study was designed to compare CaP cancer chemopreventive effects of green tea polyphenols (GTP), water extract of black tea, and their major constituents epigallocatechin-3-gallate and theaflavins, respectively, in athymic nude mice implanted with androgen-sensitive human CaP CWR22Rnu1 cells. Our data demonstrated that the treatment with all the tea ingredients resulted in (i) significant inhibition in growth of implanted prostate tumors, (ii) reduction in the level of serum prostate specific antigen, (iii) induction of apoptosis accompanied with upregulation in Bax and decrease in Bcl-2 proteins, and (iv) decrease in the levels of VEGF protein. Furthermore, we also found that GTP (0.01 or 0.05% w/v; given after establishment of CWR22Rnu1 tumor) causes a significant regression of tumors suggesting therapeutic effects of GTP at human achievable concentrations.
CitationCarcinogenesis 2006, 27 (4):833-839
DescriptionDietary modulation of cancer & cancer biomarkers Dietary item or component studied: green tea polyphenols (GTP), water extract of black tea, and their major constituents epigallocatechin-3-gallate and theaflavins, respectivelyOutcome studied (cancer or cancer biomarker): Cancer of the prostate gland (CaP)Study type (in vitro, animals, humans): male athymic nude miceMode of exposure (if in vivo): administration through waterImpact on outcome (including dose-response): GTP, BTE and TF mice compared with untreated mice were statistically significant with P < 0.01 according to a log-rank analysisGTP treatment was most effective among the agents tested (P < 0.001).PSA in control animals was found to be 13.95 ± 0.82 ng/ml; animals treated with GTP, BTE, EGCG and TF, the PSA levels were found to decrease significantly to 4.95 ± 1.23, 6.37 ± 1.75, 4.07 ± 0.98 and 5.9 ± 0.78 ng/ml, respectively (P < 0.01).At day 24, the level of PSA in control was 26.4 ± 1.32 ng/ml; in animals treated with GTP, BTE, EGCG and TF, the PSA levels were significantly decrease respectively to 4.46 ± 1.32, 8.85 ± 2.32, 5.7 ± 0.58 and 6.9 ± 1.32 ng/ml (P < 0.01). KEYWORDS CLASSIFICATION: analogs & derivatives;Animals;Anticarcinogenic Agents;Apoptosis;bcl-2-Associated X Protein;biosynthesis;Biflavonoids;chemistry;Catechin;drug effects;Dermatology;dietary modulation of cancer & cancer biomarkers;dietary modulation of carcinogenesis-related pathways;Flavonoids;Male;Mice;Mice,Nude;pharmacology;prevention & control;Phenols;Prostate-Specific Antigen;Prostatic Neoplasms;Proteins;Proto-Oncogene Proteins;Proto-Oncogene Proteins c-bcl-2;Research;secretion;Tea;Up-Regulation;