title: Green tea polyphenol causes differential oxidative environments in tumor versus normal epithelial cells.
abstract: 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.
authors.affiliation: Kochi Medical School, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Stephen
authors.initials: S
authors.lastname: Hsu
authors.forename: Jill
authors.initials: J
authors.lastname: Lewis
authors.forename: John
authors.initials: J
authors.lastname: Wataha
authors.forename: Douglas
authors.initials: D
authors.lastname: Dickinson
authors.forename: Baldev
authors.initials: B
authors.lastname: Singh
authors.forename: Wendy B
authors.initials: WB
authors.lastname: Bollag
authors.forename: Petra
authors.initials: P
authors.lastname: Lockwood
authors.forename: Eisaku
authors.initials: E
authors.lastname: Ueta
authors.forename: Tokio
authors.initials: T
authors.lastname: Osaki
authors.forename: George
authors.initials: G
authors.lastname: Schuster
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005419:Flavonoids; D006801:Humans; D009369:Neoplasms; D018384:Oxidative Stress / Q000187:drug effects*; D010636:Phenols / Q000494:pharmacology; D011108:Polymers / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D013662:Tea / Q000737:chemistry*; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000975:Antioxidants; D005419:Flavonoids; D010636:Phenols; D011108:Polymers; D017382:Reactive Oxygen Species; D013662:Tea; D013778:Tetrazolium Salts; D013844:Thiazoles; D002392:Catechin; C045651:epigallocatechin gallate; D002374:Catalase; D013482:Superoxide Dismutase; C022616:thiazolyl blue; D001973:Bromodeoxyuridine