Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 이인혜 | * |
dc.date.accessioned | 2019-08-22T16:30:08Z | - |
dc.date.available | 2019-08-22T16:30:08Z | - |
dc.date.issued | 2019 | * |
dc.identifier.issn | 0023-6837 | * |
dc.identifier.issn | 1530-0307 | * |
dc.identifier.other | OAK-25234 | * |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/251229 | - |
dc.description.abstract | Doxorubicin is a widely used DNA damage-inducing anti-cancer drug. However, its use is limited by its dose-dependent side effects, such as cardiac toxicity. Cholesterol-lowering statin drugs increase the efficacy of some anti-cancer drugs. Cholesterol is important for cell growth and a critical component of lipid rafts, which are plasma membrane microdomains important for cell signaling. 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMG-CR) is a critical enzyme in cholesterol synthesis. Here, we show that doxorubicin downregulated HMG-CR protein levels and thus reduced levels of cholesterol and lipid rafts. Cholesterol addition attenuated doxorubicin-induced cell death, and cholesterol depletion enhanced it. Reduction of HMG-CR activity by simvastatin, a statin that acts as an HMG-CR inhibitor, or by siRNA-mediated HMG-CR knockdown enhanced doxorubicin cytotoxicity. Doxorubicin-induced HMG-CR downregulation was associated with inactivation of the EGFR-Src pathway. Furthermore, a high-cholesterol-diet attenuated the anti-cancer activity of doxorubicin in a tumor xenograft mouse model. In a multivulva model of Caenorhabditis elegans expressing an active-EGFR mutant, doxorubicin decreased hyperplasia more efficiently in the absence than in the presence of cholesterol. These data indicate that EGFR/Src/HMG-CR is a new pathway mediating doxorubicin-induced cell death and that cholesterol control could be combined with doxorubicin treatment to enhance efficacy and thus reduce side effects. | * |
dc.language | English | * |
dc.publisher | NATURE PUBLISHING GROUP | * |
dc.title | Anti-cancer effect of doxorubicin is mediated by downregulation of HMG-Co A reductase via inhibition of EGFR/Src pathway | * |
dc.type | Article | * |
dc.relation.issue | 8 | * |
dc.relation.volume | 99 | * |
dc.relation.index | SCIE | * |
dc.relation.index | SCOPUS | * |
dc.relation.startpage | 1157 | * |
dc.relation.lastpage | 1172 | * |
dc.relation.journaltitle | LABORATORY INVESTIGATION | * |
dc.identifier.doi | 10.1038/s41374-019-0193-1 | * |
dc.identifier.wosid | WOS:000477777000006 | * |
dc.identifier.scopusid | 2-s2.0-85060907934 | * |
dc.author.google | Yun, Un-Jung | * |
dc.author.google | Lee, Ji-Hye | * |
dc.author.google | Shim, Jaegal | * |
dc.author.google | Yoon, Kyungsil | * |
dc.author.google | Goh, Sung-Ho | * |
dc.author.google | Yi, Eun Hee | * |
dc.author.google | Ye, Sang-Kyu | * |
dc.author.google | Lee, Jae-Seon | * |
dc.author.google | Lee, Hyunji | * |
dc.author.google | Park, Jongsun | * |
dc.author.google | Lee, In Hye | * |
dc.author.google | Kim, Yong-Nyun | * |
dc.contributor.scopusid | 이인혜(26531358400) | * |
dc.date.modifydate | 20240220125349 | * |