title: Safety and chemopreventive effect of Polyphenon E in preventing early and metastatic progression of prostate cancer in TRAMP mice.
abstract: 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 transgenic adenocarcinoma of the mouse prostate (TRAMP) mice. A total of 119 male TRAMP and 119 C57BL/6J mice were treated orally with one of 3 doses of Polyphenon E (200, 500, and 1,000 mg/kg/day) in drinking water ad libitum replicating human achievable doses. Baseline assessments were performed before treatments. Safety and efficacy assessments during treatments were performed when mice were 12, 22, and 32 weeks old. The number and size of tumors in treated TRAMP mice were significantly decreased compared with untreated animals. In untreated 32 weeks old TRAMP mice, prostate carcinoma metastasis to distant sites was observed in 100% of mice (8/8), compared with 13% of mice (2/16) treated with high-dose Polyphenon E during the same period. Furthermore, 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. 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. Our findings provide additional evidence for the safety and chemopreventive effect of Polyphenon E in preventing metastatic progression of prostate cancer.
authors: Department of Cancer Epidemiology, Moffitt Cancer Center, University of South Florida, College of Medicine, 12902 Magnolia Drive, Tampa, FL 33612. Jong.Park@moffitt.org.
authors: Seung Joon
authors: SJ
authors: Kim
authors: Ernest
authors: E
authors: Amankwah
authors: Shahnjayla
authors: S
authors: Connors
authors: Hyun Y
authors: HY
authors: Park
authors: Maria
authors: M
authors: Rincon
authors: Heather
authors: H
authors: Cornnell
authors: Ganna
authors: G
authors: Chornokur
authors: Arig Ibrahim
authors: AI
authors: Hashim
authors: Junsung
authors: J
authors: Choi
authors: Ya-Yu
authors: YY
authors: Tsai
authors: Robert W
authors: RW
authors: Engelman
authors: Nagi
authors: N
authors: Kumar
authors: Jong Y
authors: JY
authors: Park
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012449:Safety
chemical_list: D002392:Catechin; C472086:polyphenon E