Safety and chemopreventive effect of Polyphenon E in preventing early and metastatic progression of prostate cancer in TRAMP mice
Menée sur un modèle murin, cette étude évalue la toxicité du polyphénon E (un extrait de thé vert) ainsi que son efficacité pour prévenir la progession d'un cancer de la prostate et le risque de métastase
Background : Prostate cancer treatment is often accompanied by untoward side effects. Therefore, chemoprevention to reduce the risk and inhibit the progression of prostate cancer may be an effective approach to reducing disease burden. We investigated the safety and efficacy of Polyphenon E, a green tea extract, in reducing the progression of prostate cancer in TRAMP mice. Methods : 119 male TRAMP and 119 C57BL/6J mice were treated orally with one of three doses of Polyphenon E (200, 500, 1,000 mg/kg/day) in drinking water ad libitum replicating human achievable doses. Baseline assessments were performed prior to treatments. Safety and efficacy assessments during treatments were performed when mice were 12, 22 and 32 weeks old. Results : The number and size of tumors in treated TRAMP mice were significantly decreased compared to untreated animals. In untreated 32 weeks old TRAMP mice, prostate carcinoma metastasis to distant sites was observed in 100% of mice (8/8), compared to 13% of mice (2/16) treated with high dose Polyphenon E during the same period. Further, Polyphenon E treatment significantly inhibited metastasis in TRAMP mice in a dose-dependent manner (P=0.0003). Long-term (32 weeks) treatment with Polyphenon E was safe and well tolerated with no evidence of toxicity in C57BL/6J mice. Conclusions : Polyphenon E is an effective chemopreventive agent in preventing the progression of prostate cancer to metastasis in TRAMP mice. Polyphenon E showed no toxicity in these mouse models. Impact : Our findings provide additional evidence for the safety and chemopreventive effect of Polyphenon E in preventing progression of PCa.