Safety and chemopreventive effect of polyphenon E in preventing early and metastatic progression of prostate cancer in TRAMP mice

Seung Joon Kim, Ernest Amankwah, Shahnjayla Connors, Hyun Y. Park, Maria Rincon, Heather Cornnell, Ganna Chornokur, Arig Ibrahim Hashim, Junsung Choi, Ya Yu Tsai, Robert W. Engelman, Nagi Kumar, Jong Y. Park

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)435-444
Number of pages10
JournalCancer Prevention Research
Volume7
Issue number4
DOIs
StatePublished - 2014
Externally publishedYes

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Transgenic Mice
Prostate
Prostatic Neoplasms
Adenocarcinoma
Safety
Neoplasm Metastasis
Inbred C57BL Mouse
Therapeutics
polyphenon E
Chemoprevention
Tea
Drinking Water
Carcinoma
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Safety and chemopreventive effect of polyphenon E in preventing early and metastatic progression of prostate cancer in TRAMP mice. / Kim, Seung Joon; Amankwah, Ernest; Connors, Shahnjayla; Park, Hyun Y.; Rincon, Maria; Cornnell, Heather; Chornokur, Ganna; Hashim, Arig Ibrahim; Choi, Junsung; Tsai, Ya Yu; Engelman, Robert W.; Kumar, Nagi; Park, Jong Y.

In: Cancer Prevention Research, Vol. 7, No. 4, 2014, p. 435-444.

Research output: Contribution to journalArticle

Kim, SJ, Amankwah, E, Connors, S, Park, HY, Rincon, M, Cornnell, H, Chornokur, G, Hashim, AI, Choi, J, Tsai, YY, Engelman, RW, Kumar, N & Park, JY 2014, 'Safety and chemopreventive effect of polyphenon E in preventing early and metastatic progression of prostate cancer in TRAMP mice', Cancer Prevention Research, vol. 7, no. 4, pp. 435-444. https://doi.org/10.1158/1940-6207.CAPR-13-0427-T
Kim, Seung Joon ; Amankwah, Ernest ; Connors, Shahnjayla ; Park, Hyun Y. ; Rincon, Maria ; Cornnell, Heather ; Chornokur, Ganna ; Hashim, Arig Ibrahim ; Choi, Junsung ; Tsai, Ya Yu ; Engelman, Robert W. ; Kumar, Nagi ; Park, Jong Y. / Safety and chemopreventive effect of polyphenon E in preventing early and metastatic progression of prostate cancer in TRAMP mice. In: Cancer Prevention Research. 2014 ; Vol. 7, No. 4. pp. 435-444.
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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.",
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AU - Cornnell, Heather

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AU - Hashim, Arig Ibrahim

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AU - Engelman, Robert W.

AU - Kumar, Nagi

AU - Park, Jong Y.

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AB - 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.

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