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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on September 3, 2003; DOI: 10.1124/jpet.103.054676


0022-3565/03/3071-230-236$20.00
JPET 307:230-236, 2003
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CELLULAR AND MOLECULAR

Green Tea Polyphenol Causes Differential Oxidative Environments in Tumor versus Normal Epithelial Cells

Tetsuya Yamamoto, Stephen Hsu, Jill Lewis, John Wataha, Douglas Dickinson, Baldev Singh, Wendy B. Bollag, Petra Lockwood, Eisaku Ueta, Tokio Osaki, and George Schuster

Department of Oral Biology and Maxillofacial Pathology, School of Dentistry, Medical College of Georgia, Augusta, Georgia (S.H., J.L., J.W., D.D., B.S., P.L., G.S.); Kochi Medical School, Kochi, Japan (T.Y., E.U., T.O.); and Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, Georgia (W.B.B.)

Green tea polyphenols (GTPPs) are considered beneficial to human health, especially as chemopreventive agents. Recently, cytotoxic reactive oxygen species (ROS) were identified in tumor and certain normal cell cultures incubated with high concentrations of the most abundant GTPP, (–)-epigallocatechin-3-gallate (EGCG). If EGCG also provokes the production of ROS in normal epithelial cells, it may preclude the topical use of EGCG at higher doses. The current study examined the oxidative status of normal epithelial, normal salivary gland, and oral carcinoma cells treated with EGCG, using ROS measurement and catalase and superoxide dismutase activity assays. The results demonstrated that high concentrations of EGCG induced oxidative stress only in tumor cells. In contrast, EGCG reduced ROS in normal cells to background levels. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and 5-bromodeoxyuridine incorporation data were also compared between the two oral carcinoma cell lines treated by EGCG, which suggest that a difference in the levels of endogenous catalase activity may play an important role in reducing oxidative stress provoked by EGCG in tumor cells. It is concluded that pathways activated by GTPPs or EGCG in normal epithelial versus tumor cells create different oxidative environments, favoring either normal cell survival or tumor cell destruction. This finding may lead to applications of naturally occurring polyphenols to enhance the effectiveness of chemo/radiation therapy to promote cancer cell death while protecting normal cells.


Received May 20, 2003; accepted July 1, 2003.

Address correspondence to: Dr. Stephen Hsu, Department of Oral Biology and Maxillofacial Pathology, AD1443 School of Dentistry, Medical College of Georgia, Augusta, GA 30912-1126. E-mail: shsu{at}mail.mcg.edu




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