title: Selective death of cancer cells by preferential induction of reactive oxygen species in response to (-)-epigallocatechin-3-gallate.
abstract: (-)-Epigallocatechin-3-gallate (EGCG) induces apoptosis in cancer cells without adversely affecting normal cells. Understanding the cancer-specific cytotoxic activity of EGCG is very important in defining the mechanism of tumorigenesis and identifying superb chemotherapeutic agents against cancer. We comparatively assayed human telomerase reverse transcriptase (hTERT)-mediated apoptosis by EGCG-induced reactive oxygen species (ROS) in normal cells and cancer cells. EGCG showed differential levels of ROS induction between the cell types; ROS, especially hydrogen peroxide, was highly induced in cancer cells, while it was not in normal cells. In addition, the higher level of ROS down-regulated hTERT via binding of CCCTC binding factor (CTCF) to the core promoter region of hTERT, which repressed hTERT expression. CTCF binding was epigenetically controlled by the demethylation of the previously hypermethylated site for CTCF, which was induced by down-regulation of DNA methyltransferase 1 (DNMT1). In contrast, hTERT down-regulation was not observed in normal cells. These results suggest that preferential death of cancer cells by EGCG could be caused by the cancer-specific induction of ROS and epigenetic modulation of expression of apoptosis-related genes, such as hTERT.
authors.affiliation: Department of Life Science, College of Natural Science, Chung-Ang University, Seoul 156-756, Republic of Korea.
authors.forename: Na Young
authors.initials: NY
authors.lastname: Min
authors.forename: Jin-Hong
authors.initials: JH
authors.lastname: Kim
authors.forename: Jee-Hye
authors.initials: JH
authors.lastname: Choi
authors.forename: Wen
authors.initials: W
authors.lastname: Liang
authors.forename: Young Jong
authors.initials: YJ
authors.lastname: Ko
authors.forename: Sangmyung
authors.initials: S
authors.lastname: Rhee
authors.forename: Hyoweon
authors.initials: H
authors.lastname: Bang
authors.forename: Seung Wook
authors.initials: SW
authors.lastname: Ham
authors.forename: Ae Ja
authors.initials: AJ
authors.lastname: Park
authors.forename: Kwang-Ho
authors.initials: KH
authors.lastname: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D045325:HCT116 Cells; D057809:HEK293 Cells; D006801:Humans; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D019098:Telomerase / Q000037:antagonists & inhibitors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; D050759:Cyclin-Dependent Kinase Inhibitor p21; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D002392:Catechin; C045651:epigallocatechin gallate; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; C509186:TERT protein, human; D019098:Telomerase