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 pref erentially in HeLa and human mammary adenocarcinoma by the naturally-occurr ing catechin of green tea, (-)-epigallocatechin-3-gallate (EGCg). With cell s in culture, EGCg preferentially inhibited growth of HeLa and mammary aden ocarcinoma cells compared with growth of mammary epithelial cells. Inhibite d cells became smaller, and cell death was accompanied by a condensed and f ragmented appearance of the nuclear DNA as revealed by fluorescence microsc opy with 4',6-diamidino-2-phenylindole, suggestive of apoptosis. Mammary ep ithelial cells recovered from EGCg treatment even at 50 mu M, whereas growt h of HeLa and mammary adenocarcinoma cells was inhibited by EGCg at concent rations as low as 1 mu M with repeated twice-daily additions and did not re cover from treatment with 50 mu M EGCg. The findings correlate inhibition o f cell surface NADH oxidase activity and inhibition of growth with EGCg-ind uced apoptosis. BIOCHEM PHARMACOL 60;7:937-946, 2000. (C) 2000 Elsevier Sci ence Inc.