Preferential inhibition by (-)-epigallocatechin-3-gallate of the cell surface NADH oxidase and growth of transformed cells in culture.
A drug-responsive and cancer-specific NADH oxidase of the mammalian plasma membrane, constitutively activated in transformed cells, was inhibited preferentially in HeLa and human mammary adenocarcinoma by the naturally-occurring catechin of green tea, (-)-epigallocatechin-3-gallate (EGCg). With cells in culture, EGCg preferentially inhibited growth of HeLa and mammary adenocarcinoma cells compared with growth of mammary epithelial cells. Inhibited cells became smaller, and cell death was accompanied by a condensed and fragmented appearance of the nuclear DNA as revealed by fluorescence microscopy with 4',6-diamidino-2-phenylindole, suggestive of apoptosis. Mammary epithelial cells recovered from EGCg treatment even at 50 microM, whereas growth of HeLa and mammary adenocarcinoma cells was inhibited by EGCg at concentrations as low as 1 microM with repeated twice-daily additions and did not recover from treatment with 50 microM EGCg. The findings correlate inhibition of cell surface NADH oxidase activity and inhibition of growth with EGCg-induced apoptosis.
Morré
D J
DJ
Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA. Morre@pharmacy.purdue.edu
Bridge
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Wu
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Morré
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D017209:Apoptosis; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors*; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D009097:Multienzyme Complexes; D002392:Catechin; C045651:epigallocatechin gallate; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases