Inhibition of growth and induction of apoptosis in human cancer cell lines by tea polyphenols

In order to study the biological activities of tea preparations and purified tea polyphenols, their growth inhibitory effects were investigated using four human cancer cell lines. Growth inhibition was measured by [(3)H]thymidine incorporation after 48 h of treatment. The green tea catechins (-)-epigallocatechin-3-gallate (EGCG) and (-)-epigallocatechin (EGC) displayed strong growth inhibitory effects against lung tumor cell lines H661 and H1299, with estimated IC(50) values of 22 mu M, but were less effective against lung cancer cell line H441 and colon cancer cell line MT-29 with IC(50) values 2- to 3-fold higher. (-)-Epicatechin-3-gallate, had lower activities, and (-)-epicatechin was even less effective. Preparations of green tea polyphenols and theaflavins had higher activities than extracts of green tea and decaffeinated green tea. The results suggest that the growth inhibitory activity of tea extracts is caused by the activities of different tea polyphenols, Exposure of H661 cells to 30 mu M EGCG, EGC or theaflavins for 24 h led to the induction of apoptosis as determined by an annexin V apoptosis assay, showing apoptosis indices of 23, 26 and 8%, respectively; with 100 mu M of these compounds, the apoptosis indices were 82, 76 and 78%, respectively, Incubation of H651 cells with EGCG also induced a dose-dependent formation of H(2)O(2). Addition of H(2)O(2) to H661 cells caused apoptosis in a manner similar to that caused by EGCG, The EGCG-induced apoptosis in H661 cells was completely inhibited by exogenously added catalase (50 units/ml). These results suggest that tea polyphenol-induced production of H(2)O(2) may mediate apoptosis and that this may contribute to the growth inhibitory activities of tea polyphenols in vitro.