| Epigenetic and genetic mechanisms contribute to telomerase inhibition by EGCG. | |
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MedLine Citation:
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PMID: 17570133 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The ends of human chromosomes are protected from the degradation associated with cell division by 15-20 kb long segments of hexameric repeats of 5'-TTAGGG-3' termed telomeres. In normal cells telomeres lose up to 300 bp of DNA per cell division that ultimately leads to senescence; however, most cancer cells bypass this lifespan restriction through the expression of telomerase. hTERT, the catalytic subunit essential for the proper function of telomerase, has been shown to be expressed in approximately 90% of all cancers. In this study we investigated the hTERT inhibiting effects of (-)-epigallocatechin-3-gallate (EGCG), the major polyphenol found in green tea catechins, in MCF-7 breast cancers cells and HL60 promyelocytic leukemia cells. Exposure to EGCG reduced cellular proliferation and induced apoptosis in both MCF-7 and HL60 cells in vitro, although hTERT mRNA expression was decreased only in MCF-7 cells when treated with EGCG. Furthermore, down-regulation of hTERT gene expression in MCF-7 cells appeared to be largely due to epigenetic alterations. Treatment of MCF-7 cells with EGCG resulted in a time-dependent decrease in hTERT promoter methylation and ablated histone H3 Lys9 acetylation. In conjunction with demethylation, further analysis showed an increase in hTERT repressor E2F-1 binding at the promoter. From these findings, we propose that EGCG is effective in causing cell death in both MCF-7 and HL60 cancer cell lines and may work through different pathways involving both anti-oxidant effects and epigenetic modulation. |
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Authors:
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Joel B Berletch; Canhui Liu; William K Love; Lucy G Andrews; Santosh K Katiyar; Trygve O Tollefsbol |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of cellular biochemistry Volume: 103 ISSN: 1097-4644 ISO Abbreviation: J. Cell. Biochem. Publication Date: 2008 Feb |
Date Detail:
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Created Date: 2008-01-23 Completed Date: 2008-05-01 Revised Date: 2010-08-11 |
Medline Journal Info:
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Nlm Unique ID: 8205768 Medline TA: J Cell Biochem Country: United States |
Other Details:
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Languages: eng Pagination: 509-19 Citation Subset: IM |
Copyright Information:
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(c) 2007 Wiley-Liss, Inc. |
Affiliation:
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Department of Biology, University of Alabama Birmingham, Birmingham, Alabama 35294, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenocarcinoma
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pathology Apoptosis / drug effects Breast Neoplasms / pathology Catechin / analogs & derivatives*, pharmacology Cell Division / drug effects Cell Line, Tumor / drug effects, enzymology DNA Methylation / drug effects* E2F1 Transcription Factor / metabolism Epigenesis, Genetic / drug effects* Female Gene Expression Regulation, Neoplastic / drug effects* HL-60 Cells / drug effects, enzymology Histones / metabolism Humans Lysine / metabolism Male Methylation / drug effects Neoplasm Proteins / antagonists & inhibitors*, metabolism Promoter Regions, Genetic / drug effects Protein Processing, Post-Translational / drug effects* RNA, Messenger / biosynthesis RNA, Neoplasm / biosynthesis Telomerase / antagonists & inhibitors*, genetics |
| Grant Support | |
ID/Acronym/Agency:
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R01 CA129415-01A1/CA/NCI NIH HHS; R21CA114019-OIA1/CA/NCI NIH HHS; U54 CA100949-010007/CA/NCI NIH HHS; U54 CA118948-010001/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/E2F1 Transcription Factor; 0/E2F1 protein, human; 0/Histones; 0/Neoplasm Proteins; 0/RNA, Messenger; 0/RNA, Neoplasm; 154-23-4/Catechin; 56-87-1/Lysine; 989-51-5/epigallocatechin gallate; EC 2.7.7.49/Telomerase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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