DC Field | Value | Language |
---|---|---|
dc.contributor.author | Lee, Boah | ko |
dc.contributor.author | Min, Jeong A. | ko |
dc.contributor.author | Nashed, Abdullateef | ko |
dc.contributor.author | Lee, Sang-Ok | ko |
dc.contributor.author | Yoo, Jae Cheal | ko |
dc.contributor.author | Chi, Seung-Wook | ko |
dc.contributor.author | Yi, Gwan-Su | ko |
dc.date.accessioned | 2019-07-05T05:50:04Z | - |
dc.date.available | 2019-07-05T05:50:04Z | - |
dc.date.created | 2019-07-01 | - |
dc.date.issued | 2019-06 | - |
dc.identifier.citation | BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.514, no.2, pp.518 - 523 | - |
dc.identifier.issn | 0006-291X | - |
dc.identifier.uri | http://hdl.handle.net/10203/262987 | - |
dc.description.abstract | Irinotecan is a strong anticancer drug whose mechanismof action has been reported only for the inhibition of DNA topoisomerase I (Topo I) through its active metabolite SN-38. In this study, we present a new mechanism of Irinotecan which inhibits the activities of MDM2, an E3 ligase of tumour suppressor p53, and Bcl-xL, an anti-apoptotic protein, through direct binding. In our structure modelling study, Irinotecan could fit to the binding sites of MDM2 and Bcl-xL for their known drugs, Nutlin-3 and ABT-737, with a better binding affinity than to Topo I. The direct binding of Irinotecan to both proteins was confirmed through a NMR study. We further showed that Irinotecan increased the amount of p53 only in the presence of MDM2 and inhibited the physical interaction of Bcl-xL with Bim, a core pro-apoptotic protein. In addition, we demonstrated that Irinotecan induced the down regulation of proliferation and strong G2/M arrest in HCT116 colon cancer cells shortly after treatment. Collectively, we suggest a new mechanism of action for Irinotecan as a dual target inhibitor of MDM2 and Bcl-xL facilitating the anticancer activities mediated by p53 and Bcl-xL interaction partners. (C) 2019 Elsevier Inc. All rights reserved. | - |
dc.language | English | - |
dc.publisher | ACADEMIC PRESS INC ELSEVIER SCIENCE | - |
dc.title | A novel mechanism of irinotecan targeting MDM2 and Bcl-xL | - |
dc.type | Article | - |
dc.identifier.wosid | 000470803700025 | - |
dc.identifier.scopusid | 2-s2.0-85066111430 | - |
dc.type.rims | ART | - |
dc.citation.volume | 514 | - |
dc.citation.issue | 2 | - |
dc.citation.beginningpage | 518 | - |
dc.citation.endingpage | 523 | - |
dc.citation.publicationname | BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | - |
dc.identifier.doi | 10.1016/j.bbrc.2019.04.009 | - |
dc.contributor.localauthor | Yi, Gwan-Su | - |
dc.contributor.nonIdAuthor | Min, Jeong A. | - |
dc.contributor.nonIdAuthor | Lee, Sang-Ok | - |
dc.contributor.nonIdAuthor | Chi, Seung-Wook | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | Irinotecan | - |
dc.subject.keywordAuthor | Dual-targets | - |
dc.subject.keywordAuthor | MDM2 | - |
dc.subject.keywordAuthor | Bcl-xL | - |
dc.subject.keywordAuthor | Structure modelling | - |
dc.subject.keywordAuthor | NMR | - |
dc.subject.keywordPlus | TOPOISOMERASE-I | - |
dc.subject.keywordPlus | P53 | - |
dc.subject.keywordPlus | ANTAGONISTS | - |
dc.subject.keywordPlus | INHIBITORS | - |
dc.subject.keywordPlus | ABT-737 | - |
dc.subject.keywordPlus | LIGASE | - |
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