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Chloroquine enhances TRAIL-mediated apoptosis through up-regulation of DR5 by stabilization of mRNA and protein in cancer cells

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dc.contributor.authorPark, EJ-
dc.contributor.authorMin, KJ-
dc.contributor.authorChoi, KS-
dc.contributor.authorKubatka, P-
dc.contributor.authorKruzliak, P-
dc.contributor.authorKim, DE-
dc.contributor.authorKwon, TK-
dc.date.accessioned2018-05-04T00:24:06Z-
dc.date.available2018-05-04T00:24:06Z-
dc.date.issued2016-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/14801-
dc.description.abstractChloroquine (CQ), an anti-malarial drug, has immune-modulating activity and lysosomotropic activity. In this study, we investigated CQ sensitizes TRAIL-mediated apoptosis in human renal cancer Caki cells. Combination of CQ and TRAIL significantly induces apoptosis in human renal cancer Caki cells and various human cancer cells, but not in normal mouse kidney cells (TMCK-1) and human mesangial cells (MC). CQ up-regulates DR5 mRNA and protein expression in a dose- and time- dependent manner. Interestingly, CQ regulates DR5 expression through the increased stability in the mRNA and protein of DR5, rather than through the increased transcriptional activity of DR5. Moreover, we found that CQ decreased the expression of Cbl, an E3 ligase of DR5, and knock-down of Cbl markedly enhanced DR5 up-regulation. Other lysosomal inhibitors, including monensin and nigericin, also up-regulated DR5 and sensitized TRAIL-mediated apoptosis. Therefore, this study demonstrates that lysosomal inhibition by CQ may sensitize TRAIL-mediated apoptosis in human renal cancer Caki cells via DR5 up-regulation.-
dc.language.isoen-
dc.subject.MESHAnimals-
dc.subject.MESHApoptosis-
dc.subject.MESHCell Line, Tumor-
dc.subject.MESHChloroquine-
dc.subject.MESHGene Expression Regulation, Neoplastic-
dc.subject.MESHGene Knockdown Techniques-
dc.subject.MESHHumans-
dc.subject.MESHKidney Neoplasms-
dc.subject.MESHLysosomes-
dc.subject.MESHMice-
dc.subject.MESHProto-Oncogene Proteins c-cbl-
dc.subject.MESHRNA, Messenger-
dc.subject.MESHReceptors, TNF-Related Apoptosis-Inducing Ligand-
dc.subject.MESHTNF-Related Apoptosis-Inducing Ligand-
dc.titleChloroquine enhances TRAIL-mediated apoptosis through up-regulation of DR5 by stabilization of mRNA and protein in cancer cells-
dc.typeArticle-
dc.identifier.pmid26964637-
dc.identifier.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4786792/-
dc.contributor.affiliatedAuthor최, 경숙-
dc.type.localJournal Papers-
dc.identifier.doi10.1038/srep22921-
dc.citation.titleScientific reports-
dc.citation.volume6-
dc.citation.date2016-
dc.citation.startPage22921-
dc.citation.endPage22921-
dc.identifier.bibliographicCitationScientific reports, 6. : 22921-22921, 2016-
dc.identifier.eissn2045-2322-
dc.relation.journalidJ020452322-
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
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