Development of effective chemopreventive agents against
prostate cancer (CaP) for humans requires conclusive evidence of their efficacy in animal models that closely emulates human disease. The autochthonous transgenic
adenocarcinoma of the mouse prostate (TRAMP) model, which spontaneously develops metastatic CaP, is one such model that mimics progressive forms of human disease. Employing male TRAMP mice, we show that oral infusion of a polyphenolic fraction isolated from
green tea (
GTP) at a human achievable dose (equivalent to six cups of
green tea per day) significantly inhibits CaP development and increases survival in these mice. In two separate experiments, the cumulative incidence of palpable
tumors at 32 weeks of age in 20 untreated mice was 100% (20 of 20). In these mice, 95% (19 of 20), 65% (13 of 20), 40% (8 of 20), and 25% (5 of 20) of the animals exhibited distant site
metastases to lymph nodes, lungs, liver, and bone, respectively. However, 0.1%
GTP (wt/vol) provided as the sole source of drinking fluid to TRAMP mice from 8 to 32 weeks of age resulted in (i) significant delay in primary
tumor incidence and
tumor burden as assessed sequentially by MRI, (ii) significant decrease in prostate (64%) and genitourinary (GU) (72%) weight, (iii) significant inhibition in serum
insulin-like growth factor-I and restoration of
insulin-like growth factor binding protein-3 levels, and (iv) marked reduction in the
protein expression of
proliferating cell nuclear antigen (
PCNA) in the prostate compared with water-fed TRAMP mice. The striking observation of this study was that
GTP infusion resulted in almost complete inhibition of distant site
metastases. Furthermore,
GTP consumption caused significant apoptosis of CaP cells, which possibly resulted in reduced dissemination of
cancer cells, thereby causing inhibition of
prostate cancer development, progression, and
metastasis of CaP to distant organ sites.