0 199

Cited 32 times in

Cyclic induction of senescence with intermittent AZT treatment accelerates both apoptosis and telomere loss

DC FieldValueLanguage
dc.contributor.author라선영-
dc.contributor.author안성환-
dc.contributor.author양상화-
dc.contributor.author정현철-
dc.contributor.author정희철-
dc.contributor.author지현정-
dc.date.accessioned2017-10-26T06:18:43Z-
dc.date.available2017-10-26T06:18:43Z-
dc.date.issued2005-
dc.identifier.issn0167-6806-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/150782-
dc.description.abstractBACKGROUND: 3'-azido-2',3'-dideoxythymidine (AZT) is phosphorylated intracellularly to 3'-azido-3'-deoxythymidine-5'-triphosphate (AZT-TP), which is incorporated into telomeric DNA, thereby blocking chain elongation. AZT is also known to inhibit reverse transcriptase, as well as other cellular enzymes including DNA polymerase gamma, thymidine kinase, and telomerase. METHODS: We induced cancer cell senescence by treating MCF-7 cells with AZT in dosages of IC10 and IC20 for an extended period (about 120 population doublings (PD)). We then investigated the sequential changes in cellular growth, expression of telomerase subunits and transcription factors (c-Myc, Mad1), telomerase activity and telomere length. RESULTS: Senescence, apoptosis, growth delay, inhibition of telomerase activity and shortening of telomere length were all observed in a dose- and time-dependent manner. After the onset of senescence, the apoptosis rate increased slowly during early PDs. In contrast to senescence, the apoptotic rate showed little change after AZT removal, while it increased suddenly and significantly in a dose-dependent manner upon the second introduction of AZT. Continuous shortening of the telomeric length was observed with AZT, and, upon re-exposure to AZT, shortening of the telomere occurred more rapidly than with first exposure. Of the telomerase subunits, telomerase reverse transcriptase (hTERT) and c-Myc were the first to show a reduction in activity after AZT treatment, followed by changes in hTER , Mad1 and hTEP-1. CONCLUSION: Cyclic treatment with AZT initially suppressed hTERT and c-Myc, followed by suppression of hTER, Mad1 and hTEP-1. Furthermore, the treatment accelerated both telomere loss and apoptosis, even when administered at a senescence-inducing dosage level.-
dc.description.statementOfResponsibilityrestriction-
dc.languageEnglish-
dc.publisherKluwer Academic-
dc.relation.isPartOfBREAST CANCER RESEARCH AND TREATMENT-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHApoptosis/drug effects*-
dc.subject.MESHBreast Neoplasms/drug therapy*-
dc.subject.MESHCellular Senescence/drug effects-
dc.subject.MESHCellular Senescence/genetics-
dc.subject.MESHDNA-Binding Proteins/drug effects-
dc.subject.MESHDNA-Binding Proteins/metabolism-
dc.subject.MESHDose-Response Relationship, Drug-
dc.subject.MESHGene Expression/drug effects-
dc.subject.MESHHumans-
dc.subject.MESHReverse Transcriptase Inhibitors/pharmacology*-
dc.subject.MESHTelomerase/drug effects*-
dc.subject.MESHTelomerase/genetics-
dc.subject.MESHTelomerase/metabolism-
dc.subject.MESHTelomere/drug effects*-
dc.subject.MESHTelomere/metabolism-
dc.subject.MESHTelomere/ultrastructure-
dc.subject.MESHTranscription Factors/drug effects-
dc.subject.MESHTranscription Factors/metabolism-
dc.subject.MESHTumor Cells, Cultured-
dc.subject.MESHZidovudine/pharmacology*-
dc.titleCyclic induction of senescence with intermittent AZT treatment accelerates both apoptosis and telomere loss-
dc.typeArticle-
dc.publisher.locationNetherlands-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.collegeResearch Institutes (연구소)-
dc.contributor.collegeResearch Institutes (연구소)-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Internal Medicine (내과학교실)-
dc.contributor.departmentCancer Metastasis Research Center (암전이연구센터)-
dc.contributor.departmentCancer Metastasis Research Center (암전이연구센터)-
dc.contributor.departmentDept. of Internal Medicine (내과학교실)-
dc.contributor.departmentDept. of Internal Medicine (내과학교실)-
dc.contributor.departmentYonsei Biomedical Research Center (연세의생명연구원)-
dc.contributor.googleauthorHyun Jung Ji-
dc.contributor.googleauthorSun Young Rha-
dc.contributor.googleauthorHei Cheul Jeung-
dc.contributor.googleauthorSang Hwa Yang-
dc.contributor.googleauthorSung Whan An-
dc.contributor.googleauthorHyun Cheol Chung-
dc.identifier.doi10.1007/s10549-005-5156-0-
dc.contributor.localIdA01316-
dc.contributor.localIdA02239-
dc.contributor.localIdA02288-
dc.contributor.localIdA03773-
dc.contributor.localIdA03794-
dc.contributor.localIdA03972-
dc.relation.journalcodeJ00403-
dc.identifier.eissn1573-7217-
dc.identifier.pmid16132531-
dc.identifier.urlhttp://link.springer.com/article/10.1007%2Fs10549-005-5156-0-
dc.subject.keywordapoptosis-
dc.subject.keywordhTERT-
dc.subject.keywordsenescence-
dc.subject.keywordtelomerase-
dc.subject.keywordtelomere-
dc.contributor.alternativeNameRha, Sun Young-
dc.contributor.alternativeNameAn, Sung Whan-
dc.contributor.alternativeNameYang, Sang Hwa-
dc.contributor.alternativeNameChung, Hyun Cheol-
dc.contributor.alternativeNameJeung, Hei Cheul-
dc.contributor.alternativeNameJee, Hyun Joong-
dc.citation.volume93-
dc.citation.number3-
dc.citation.startPage227-
dc.citation.endPage236-
dc.identifier.bibliographicCitationBREAST CANCER RESEARCH AND TREATMENT, Vol.93(3) : 227-236, 2005-
dc.date.modified2017-05-04-
Appears in Collections:
5. Research Institutes (연구소) > Cancer Metastasis Research Center (암전이연구센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.