Telomerase inhibition, telomere shortening, and senescence of cancer cells by tea catechins.
Animal in vivo studies and human epidemiological observations indicated potent anticancer effects for tea. Here we demonstrate that epigallocatechin gallate (EGCG), a major tea catechin, strongly and directly inhibits telomerase, an enzyme essential for unlocking the proliferative capacity of cancer cells by maintaining the tips of their chromosomes. Telomerase inhibition was elaborated in a cell-free system (cell extract) as well as in living cells. In addition, the continued growth of two representative human cancer cell lines, U937 monoblastoid leukemia cells and HT29 colon adenocarcinoma cells, in the presence of nontoxic concentrations of EGCG showed life span limitations accompanied with telomere shortening, chromosomal abnormalities, and expression of the senescence-associated beta-galactosidase. It is suggested that telomerase inhibition could be one of the major mechanisms underlying the anticancer effects of tea.
Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Kami-Ikebukuro, Tokyo, Toshima-ku, 170-8455, Japan. inaasani@ns.jfcr.or.jp
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Seimiya
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Tsuruo
D000230:Adenocarcinoma; D000970:Antineoplastic Agents / Q000494:pharmacology; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002474:Cell-Free System; D016922:Cellular Senescence / Q000187:drug effects*; D003110:Colonic Neoplasms; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D007948:Leukemia, Monocytic, Acute; D009369:Neoplasms / Q000473:pathology*; D013662:Tea / Q000737:chemistry*; D019098:Telomerase / Q000037:antagonists & inhibitors*; D016615:Telomere / Q000187:drug effects* / Q000648:ultrastructure; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase / Q000032:analysis
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate; D019098:Telomerase; D001616:beta-Galactosidase