6071

The low prostate cancer rates in countries where consumption of green tea is high suggests green tea may be protective against this human cancer. Green and black tea and some tea catechins, including epigallocatechin gallate (EGCG), have shown anticancer properties in vitro and in vivo. Inhibition of prostate tumor development in the TRAMP model by administration of a green tea polyphenolic fraction in drinking water has been reported (2001, PNAS 98:10350-5). However, we observed that green tea extract does not affect the in vivo growth of rat prostate cancer cells and a human prostate xenograft (Proc AACR 44, Abstract #3895, 2003). In this study, we examined the effect of a green tea extract developed by Unilever Bestfoods for human clinical trials on the induction of prostate cancer in a rat model. Hormone-dependent prostate cancers were induced in male Wistar-Unilever (Hsd:WU) rats by the following treatment. To stimulate prostatic cell proliferation, rats were first treated with Flutamide (20 mg/day for 21 days by gavage) followed one day later by testosterone propionate (100 mg/kg/day by single s.c. injection). Sixty hours after this androgen injection, rats (34 per group) received a single intravenous injection of N-methyl-N-nitrosourea (MNU [NCI Carcinogen Repository]; 30 mg/kg body weight). Beginning one week post-MNU, low dose chronic androgen stimulation was provided by two 3 cm-long subcutaneous Silastic tubing capsules containing crystalline testosterone; capsules were replaced once after 9 months. One week post-MNU, animals began receiving drinking water supplemented with either a 1.5% solution of green tea extract (735 mg/L EGCG, 1656 mg/L total catechins, and 300 mg/L caffeine) or a solution of 300 mg/L caffeine, or they continued to receive plain drinking water. Growth and survival were not affected by the treatments, but rats on the tea extract drank 16% less than rats on caffeine or control rats which drank identical amounts. The two treatments did not affect prostate cancer induction. In comparison to a total cancer incidence of 64% (all accessory sex glands) in control rats, total cancer incidences of 60% and 58% were observed in groups given the tea extract or caffeine, respectively. Similarly, cancers that were clearly confined to the dorsolateral/anterior prostate were found in 55% of controls versus 40% and 42% of rats in groups given the tea extract or caffeine, respectively. Adding data on carcinoma in situ to this did not change the observed lack of a protective effect. Using cyproterone acetate in stead of Flutamide or MNU from Ash Stevens did not substantially change prostate cancer incidence in parallel groups given drinking water. Cancer incidence in only the seminal vesicle was less than 15% in all groups. These data do not support the hypothesis that green tea is an inhibitor of prostate carcinogenesis and they are in line with our previous observations. (Supported by NIH Grant CA76426)

[Proc Amer Assoc Cancer Res, Volume 46, 2005]