Preventive effects of polyphenon E on urinary bladder and mammary cancers in rats and correlations with serum and urine levels of tea polyphenols.
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 50 x to 1,000 x 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.
Lubet
Ronald A
RA
National Cancer Institute, Executive Plaza North, Suite 2110, 6130 Executive Boulevard, Bethesda, MD 20852, USA. lubetr@mail.nih.gov
Yang
Chung S
CS
Lee
Mao-Jung
MJ
Hara
Yukihiko
Y
Kapetanovic
Izet M
IM
Crowell
James A
JA
Steele
Vernon E
VE
Juliana
M Margaret
MM
Grubbs
Clinton J
CJ
D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D005419:Flavonoids / Q000097:blood* / Q000737:chemistry / Q000652:urine*; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000517:prevention & control*; D010636:Phenols / Q000097:blood* / Q000737:chemistry / Q000652:urine*; D059808:Polyphenols; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D013662:Tea / Q000737:chemistry*; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000517:prevention & control*
D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D013662:Tea; D002392:Catechin; C472086:polyphenon E