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 andpurified tea polyphenols, their growth inhibitory effects were investigatedusing four human cancer cell lines. Growth inhibition was measured by[3H]thymidine incorporation after 48 h of treatment. The green teacatechins (-)-epigallocatechin-3-gallate (EGCG) and (-)- epigallocatechin(EGC) displayed strong growth inhibitory effects against lung tumor celllines H661 and H1299, with estimated IC50 values of 22 microM, but wereless effective against lung cancer cell line H441 and colon cancer cellline HT-29 with IC50 values 2- to 3- fold higher.(-)-Epicatechin-3-gallate, had lower activities, and (-)- epicatechin waseven less effective. Preparations of green tea polyphenols and theaflavinshad higher activities than extracts of green tea and decaffeinated greentea. The results suggest that the growth inhibitory activity of teaextracts is caused by the activities of different tea polyphenols. Exposureof H661 cells to 30 microM EGCG, EGC or theaflavins for 24 h led to theinduction of apoptosis as determined by an annexin V apoptosis assay,showing apoptosis indices of 23, 26 and 8%, respectively; with 100 microMof these compounds, the apoptosis indices were 82, 76 and 78%,respectively. Incubation of H661 cells with EGCG also induced adose-dependent formation of H2O2. Addition of H2O2 to H661 cells causedapoptosis in a manner similar to that caused by EGCG. The EGCG-inducedapoptosis in H661 cells was completely inhibited by exogenously addedcatalase (50 units/ml). These results suggest that tea polyphenol-inducedproduction of H2O2 may mediate apoptosis and that this may contribute tothe growth inhibitory activities of tea polyphenols in vitro.