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SHORT COMMUNICATION

DOSE-DEPENDENT LEVELS OF EPIGALLOCATECHIN-3-GALLATE IN HUMAN COLON CANCER CELLS AND MOUSE PLASMA AND TISSUES

Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey

Epigallocatechin-3-gallate (EGCG; molecular formula: C₂₂H₁₈0₁₁)is the most abundant catechin in green tea (Camellia sinensis Theaceae). Both EGCG and green tea have been shown to have cancer-preventive activity in a number of animal models, and numerous mechanisms have been proposed based on studies with human cell lines. EGCG has been shown to undergo extensive biotransformation to yield methylated and glucuronidated metabolites in mice, rats, and humans. In the present study, we determined the concentration-dependent uptake of EGCG by HT-29 human colon cancer cells (20–600 µM) and the dose dependence of EGCG plasma and tissue levels after a single dose of EGCG (50–2000 mg/kg i.g.) to male CF-1 mice. The cytosolic levels of EGCG were linear with respect to extracellular concentration of EGCG after treatment of HT-29 cells for 2 h (915.3–6851.6 µg/g). In vivo, EGCG exhibited a linear dose relationship in the plasma (0.03–4.17 µg/ml), prostate (0.01–0.91 µg/g), and liver (0.09-18.3 µg/g). In the small intestine and colon, however, the levels of EGCG plateaued between 500 and 2000 mg/kg i.g. These results suggest that absorption of EGCG from the small intestine is largely via passive diffusion; however, at high concentrations, the small intestinal and colonic tissues become saturated. The levels of 4''-O-methyl-EGCG and 4',4''-di-O-methyl-EGCG parallel those of EGCG with respect to dose. The present study provides information with respect to what concentrations of EGCG are achievable in mice and may guide dose selection for future cancer chemoprevention studies with EGCG.

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