Sensitization of multidrug-resistant human cancer cells to Hsp90 inhibitors by down-regulation of SIRT1
DC Field | Value | Language |
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dc.contributor.author | Kim, Hak-Bong | - |
dc.contributor.author | Lee, Su-Hoon | - |
dc.contributor.author | Um, Jee-Hyun | - |
dc.contributor.author | Oh, Won Keun | - |
dc.contributor.author | Kim, Dong-Wan | - |
dc.contributor.author | Kang, Chi-Dug | - |
dc.contributor.author | Kim, Sun-Hee | - |
dc.date.available | 2020-02-28T07:42:45Z | - |
dc.date.created | 2020-02-06 | - |
dc.date.issued | 2015-11-03 | - |
dc.identifier.issn | 1949-2553 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/9916 | - |
dc.description.abstract | The effectiveness of Hsp90 inhibitors as anticancer agents was limited in multidrug-resistant (MDR) human cancer cells due to induction of heat shock proteins (Hsps) such as Hsp70/Hsp27 and P-glycoprotein (P-gp)-mediated efflux. In the present study, we showed that resistance to Hsp90 inhibitors of MDR human cancer cells could be overcome with SIRT1 inhibition. SIRT1 knock-down or SIRT1 inhibitors (amurensin G and EX527) effectively suppressed the resistance to Hsp90 inhibitors (17-AAG and AUY922) in several MDR variants of human lymphoblastic leukemia and human breast cancer cell lines. SIRT1 inhibition down-regulated the expression of heat shock factor 1 (HSF1) and subsequently Hsps and facilitated Hsp90 multichaperone complex disruption via hyperacetylation of Hsp90/Hsp70. These findings were followed by acceleration of ubiquitin ligase CHIP-mediated mutant p53 (mut p53) degradation and subsequent down-regulation of P-gp in 17-AAGtreated MDR cancer cells expressing P-gp and mut p53 after inhibition of SIRT1. Therefore, combined treatment with Hsp90 inhibitor and SIRT1 inhibitor could be a more effective therapeutic approach for Hsp90 inhibitor-resistant MDR cells via downregulation of HSF1/Hsps, mut p53 and P-gp. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | IMPACT JOURNALS LLC | - |
dc.relation.isPartOf | ONCOTARGET | - |
dc.subject | SHOCK-PROTEIN 90 | - |
dc.subject | MUTANT P53 | - |
dc.subject | CHAPERONE FUNCTION | - |
dc.subject | ANTILEUKEMIA ACTIVITY | - |
dc.subject | P-GLYCOPROTEIN | - |
dc.subject | BREAST-CANCER | - |
dc.subject | HEAT-SHOCK-PROTEIN-90 | - |
dc.subject | TANESPIMYCIN | - |
dc.subject | DEGRADATION | - |
dc.subject | STRESS | - |
dc.title | Sensitization of multidrug-resistant human cancer cells to Hsp90 inhibitors by down-regulation of SIRT1 | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000366111900090 | - |
dc.identifier.doi | 10.18632/oncotarget.5343 | - |
dc.identifier.bibliographicCitation | ONCOTARGET, v.6, no.34, pp.36202 - 36218 | - |
dc.identifier.scopusid | 2-s2.0-84946854565 | - |
dc.citation.endPage | 36218 | - |
dc.citation.startPage | 36202 | - |
dc.citation.title | ONCOTARGET | - |
dc.citation.volume | 6 | - |
dc.citation.number | 34 | - |
dc.contributor.affiliatedAuthor | Um, Jee-Hyun | - |
dc.type.docType | Article | - |
dc.subject.keywordAuthor | Hsp90 inhibitor | - |
dc.subject.keywordAuthor | MDR | - |
dc.subject.keywordAuthor | SIRT1 | - |
dc.subject.keywordAuthor | P-gp | - |
dc.subject.keywordAuthor | Hsp70 | - |
dc.subject.keywordPlus | SHOCK-PROTEIN 90 | - |
dc.subject.keywordPlus | MUTANT P53 | - |
dc.subject.keywordPlus | CHAPERONE FUNCTION | - |
dc.subject.keywordPlus | ANTILEUKEMIA ACTIVITY | - |
dc.subject.keywordPlus | P-GLYCOPROTEIN | - |
dc.subject.keywordPlus | BREAST-CANCER | - |
dc.subject.keywordPlus | HEAT-SHOCK-PROTEIN-90 | - |
dc.subject.keywordPlus | TANESPIMYCIN | - |
dc.subject.keywordPlus | DEGRADATION | - |
dc.subject.keywordPlus | STRESS | - |
dc.relation.journalResearchArea | Oncology | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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