Theaflavin-3-gallate and theaflavin-3'-gallate, polyphenols in black tea with prooxidant properties.
This study compared the in vitro responses of human gingival fibroblasts and of carcinoma cells derived from the tongue to theaflavin-3-gallate (TF-2A) and theaflavin-3'-gallate (TF-2B), polyphenols in black tea. The antiproliferative and cytotoxic effects of the theaflavin monomers were more pronounced to the carcinoma, than to the normal, cells. In phosphate buffer at pH 7.4, the theaflavins generated hydrogen peroxide and the superoxide anion, suggesting that their mode of toxicity may be due, in part, to the induction of oxidative stress. In a cell-free assay, TF-2A and TF-2B reacted directly with reduced glutathione (GSH), in a time- and concentration-dependent manner. Intracellular storages of GSH were depleted on treatment of the cells with the theaflavin monomers. Depletion of intracellular GSH was more extensive with TF-2A than with TF-2B and was more pronounced in the carcinoma, than in the normal, cells. The toxicities of the theaflavins were potentiated when the cells were cotreated with the GSH depleter, d,l-buthionine-[S,R]-sulfoximine. In the presence of catalase, pyruvate and divalent cobalt, all scavengers of reactive oxygen species, the cytotoxicities of the theaflavins were lessened. TF-2A and TF-2B induced lipid peroxidation in the carcinoma cells, whereas in the fibroblasts, peroxidation was evident upon exposure to TF-2A, but not to TF-2B. These studies demonstrated that the black tea theaflavin monomers, TF-2A and TF-2B, act as prooxidants and induce oxidative stress, with carcinoma cells more sensitive than normal fibroblasts.
Babich
Harvey
H
Department of Biology, Stern College for Women, Yeshiva University, New York, NY, USA. babich@yu.edu
Gottesman
Reena T
RT
Liebling
Emily J
EJ
Schuck
Alyssa G
AG
D000970:Antineoplastic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D044946:Biflavonoids / Q000494:pharmacology*; D002392:Catechin / Q000494:pharmacology*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D009055:Mouth / Q000166:cytology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D010636:Phenols / Q000494:pharmacology*; D059808:Polyphenols; D013662:Tea / Q000737:chemistry*
D000970:Antineoplastic Agents; D000975:Antioxidants; D044946:Biflavonoids; D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D013662:Tea; C088983:theaflavine gallate; D005707:Gallic Acid; D002392:Catechin; D006861:Hydrogen Peroxide; D005978:Glutathione