Coompo Research Chemicals

(-)-Epigallocatechin (EGC), one of green tea polyphenols, has been shown to inhibit growth of cancer cells. However its mechanism of action is poorly known. We show here that EGC strongly inhibited the growth of breast cancer cell lines (MCF-7 and MDA-MB-231) but not that of normal breast epithelial cells. The inhibition of breast cancer cell growth was due to an induction of apoptosis, without any change in cell cycle progression. MCF-7 cells are known to express a wild-type p53 whereas MDA-MB-231 cells express a mutated p53. The fact that EGC induced apoptosis in both these cell lines suggests that the EGC-triggered apoptosis is independent of p53 status. Moreover, neutralizing antibodies against the death receptor Fas and inhibitors of caspases, such as caspase-8 and -10, efficiently inhibited the EGC-triggered apoptosis. In addition, immunoblotting revealed that EGC treatment was correlated with a decrease in Bcl-2 and an increase in Bax level. These results suggest that EGC-triggered apoptosis in breast cancer cells requires Fas signaling.

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 potent in accumulation of S phase cells and inhibition of the S-G2 progression. In addition, EGC-mediated inhibition of S phase progression results in induction of apoptosis, as determined by sub-G1 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 G1 and G2/M populations, EGC did not induce apoptosis. Furthermore, EGC did not inhibit M-G1 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.

EGC decreased shortly after oxidation (tinh= 3420 s) and was transformed to a quinone-like compound. The addition of superoxide dismutase (SOD) reduced the chemiluminescence from EGC during oxidation. Active oxygen including superoxide anion radicals (O−2) may be produced in the case of EGC, but not in the case of EC. However, EGC has a more rapid scavenging effect on peroxyl radicals (kinh/kp= 232) than EC (kinh/kp= 41). The calculated C-H bond dissociation enthalpies (BDEs) for catechins at the C-2 position were unexpectedly low (65 kcal/mol) compared to O-H BDEs at phenolic sites (70 kcal/mol), suggesting that hydrogen at the C-2 position may be abstracted by free radicals. The authors propose the tentative antioxidative mechanisms of catechins depending on the experimental results and theoretical calculations.