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Research Articles

Preventive effects of Polyphenon E on urinary bladder and mammary cancers in rats and correlations with serum and urine levels of tea polyphenols

¹ Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland; ² Department of Chemical Biology, Rutgers University, Piscataway, New Jersey; ³ Food Research Laboratories, Mitsui Norin, LTD, Shizouka, Japan; and ⁴ Departments of Genetics and Surgery, University of Alabama at Birmingham, Birmingham, Alabama

Requests for reprints: Ronald A. Lubet, National Cancer Institute, Executive Plaza North, Suite 2110, 6130 Executive Boulevard, Bethesda, MD 20852. Phone: 301-594-0457; Fax: 301-402-0553. E-mail: lubetr{at}mail.nih.gov

Abstract

Polyphenon E, a standardized mixture of green tea polyphenols, was examined for its chemopreventive efficacy against chemically induced urinary bladder and mammary cancers. In the present study, Polyphenon E was administered after the last dose of 4-hydroxybutyl(butyl)nitrosamine, or roughly 30% of the way into the experiment. Polyphenon E (100 or 250 mg/kg body weight/d) caused a dose-dependent decrease in palpable urinary bladder tumors [low dose, 14 of 34; high dose, 6 of 35; controls, 20 of 34 (P < 0.01)]. In the mammary cancer model, Polyphenon E [333 or 1,000 mg/kg body weight (BW)/d] was administered beginning 5 days after a single dose of methylnitrosourea. In contrast to its significant efficacy in bladder tumor prevention, Polyphenon E had a minimal effect in the prevention of mammary cancers. Levels of polyphenols were determined in the urine and serum of rats. Relatively high levels of various polyphenols (and metabolites) were found in the urine. However, virtually no epigallocatechin-3-gallate was observed in the urine because of low systemic bioavailability; although it represents almost 65% of the polyphenols in Polyphenon E. Levels of polyphenols in serum were 50x to 1,000x less than were observed in urine. The bioavailability of these tea polyphenols to different organ sites may contribute to the differing preventive efficacy of Polyphenon E against urinary bladder and mammary cancers. [Mol Cancer Ther 2007;6(7):2022–8]

Grant support: National Cancer Institute contract numbers NO1-CN-43308 and NO1-CN-25115 and National Cancer Institute grants RO1-CA101240, RO1-CA096131, and PO1-CA88961.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 1/26/07; revised 5/ 1/07; accepted 5/25/07.