Dm. Smith et Qp. Dou, Green tea polyphenol epigallocatechin inhibits DNA replication and consequently induces leukemia cell apoptosis, INT J MOL M, 7(6), 2001, pp. 645-652
Consistent with the putative role of green tea in cancer prevention, tea po
lyphenols have previously been shown to inhibit tumor cell proliferation by
inducing G(1) or G(2)/M cell cycle arrests, also documented is their abili
ty to induce apoptosis (programmed cell death). However, it is unclear whet
her or not the cell cycle effects of polyphenols are related to their cell
death-inducing ability. Here we report that the tea polyphenol (-)-epigallo
catechin, (EGC) inhibits DNA replication in three leukemia cancer cell line
s, 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) c
ell population, breakage of endonuclear DNA, cleavage of poly(ADP-ribose) p
olymerase and loss of cell viability. When used in cells containing low S a
nd high G(1) and G(2)/M populations, EGC did not induce apoptosis. Furtherm
ore, 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.