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 G1 or G2/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 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.
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Drug Discovery Program, H. Lee Moffitt Cancer Center and Research Institute, Interdisciplinary Oncology Program and Department of Biochemistry and Molecular Biology, College of Medicine, University of South Florida, Tampa, FL 33612, USA.
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D017209:Apoptosis; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis* / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D020287:In Situ Nick-End Labeling; D019169:Jurkat Cells; D020014:K562 Cells; D007938:Leukemia / Q000473:pathology*; D008956:Models, Chemical; D010636:Phenols / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*; D011108:Polymers / Q000494:pharmacology*; D013662:Tea / Q000737:chemistry*; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors
D005419:Flavonoids; D010636:Phenols; D010936:Plant Extracts; D011108:Polymers; D013662:Tea; D002392:Catechin; D004247:DNA; C057580:gallocatechol; D013936:Thymidine