Mechanism of induction of apoptosis by green tea catechins and tea high-molecular-weight components

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It is known that many anti-tumor drugs have apoptosis-inducing activity and apoptosis-inducing compounds may be expected to have potential anti-tumor activity. We have found that green tea catechins and tea high-molecular-weight components have apoptosis-inducing activity. When apoptosis-inducing activity of lipid derivatives of gallic acid was examined in U937 cells, we found the importance of a gallate moiety and hydrophobic nature. We also found apoptosis-inducing activity of an ethanol soluble fraction in driselase digests of green tea residues. In the next experiment, examination of effects of tea components on expression of apoptosis-related genes suggested that the apoptosis-inducing mechanism of a black tea high-molecular-weight component was different from that of EGCG. As for the mechanism of apoptosis induction by EGCG, it was shown that EGCG bound Fas to activate caspase 8, leading to apoptosis. In the in vivo experiments, it was shown that a combination of slindac and EGCG effectively reduced the member of aberrant cript foci in an azoxmethane-induced rat colon cancer model by stimulating apoptosis. Finally, EGCG was found to affect signal transduction through a MAP kinase pathway and to repress expression of matrix metalloproteinase. Thus, the present results encourage the view that intake of green tea is beneficial for cancer prevention.