Green tea polyphenol epigallocatechin inhibits DNA replication and consequently induces leukemia cell apoptosis

Consistent with the putative role of green tea in cancer prevention, tea polyphenols have previously been shown to inhibit tumor cell proliferation by inducing G(1) or G(2)/M cell cycle arrests, also documented is their ability to induce apoptosis (programmed cell death). However, it is unclear whether or not the cell cycle effects of polyphenols are related to their cell death-inducing ability. Here we report that the tea polyphenol (-)-epigallocatechin, (EGC) inhibits DNA replication in three leukemia cancer cell lines, Jurkat T, HL-60 and K562. Among all the tested tea polyphenols, EGC was found to be the most patent in accumulation,of S phase cells and inhibition of the S-G(2) progression. In addition, EGC-mediated inhibition of S phase progression results in induction of apoptosis, as determined by sub-G(1) cell population, breakage of endonuclear DNA, cleavage of poly(ADP-ribose) polymerase and loss of cell viability. When used in cells containing low S and high G(1) and G(2)/M populations, EGC did not induce apoptosis. Furthermore, EGC did not inhibit M-G(1) transition. Our finding that EGC inhibits S phase progression that results in leukemia cell death provides a novel and plausible molecular mechanism for how green tea may inhibit the growth of rapidly proliferating neoplastic cells.