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β-Lapachone induces programmed necrosis through the RIP1-PARP-AIF-dependent pathway in human hepatocellular carcinoma SK-Hep1 cells.

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dc.contributor.authorPark, EJ-
dc.contributor.authorMin, KJ-
dc.contributor.authorLee, TJ-
dc.contributor.authorYoo, YH-
dc.contributor.authorKim, YS-
dc.contributor.authorKwon, TK-
dc.date.accessioned2015-11-17T02:03:44Z-
dc.date.available2015-11-17T02:03:44Z-
dc.date.issued2014-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/11984-
dc.description.abstractβ-Lapachone activates multiple cell death mechanisms including apoptosis, autophagy and necrotic cell death in cancer cells. In this study, we investigated β-lapachone-induced cell death and the underlying mechanisms in human hepatocellular carcinoma SK-Hep1 cells. β-Lapachone markedly induced cell death without caspase activation. β-Lapachone increased PI uptake and HMGB-1 release to extracellular space, which are markers of necrotic cell death. Necrostatin-1 (a RIP1 kinase inhibitor) markedly inhibited β-lapachone-induced cell death and HMGB-1 release. In addition, β-lapachone activated poly (ADP-ribosyl) polymerase-1(PARP-1) and promoted AIF release, and DPQ (a PARP-1 specific inhibitor) or AIF siRNA blocked β-lapachone-induced cell death. Furthermore, necrostatin-1 blocked PARP-1 activation and cytosolic AIF translocation. We also found that β-lapachone-induced reactive oxygen species (ROS) production has an important role in the activation of the RIP1-PARP1-AIF pathway. Finally, β-lapachone-induced cell death was inhibited by dicoumarol (a NQO-1 inhibitor), and NQO1 expression was correlated with sensitivity to β-lapachone. Taken together, our results demonstrate that β-lapachone induces programmed necrosis through the NQO1-dependent ROS-mediated RIP1-PARP1-AIF pathway.-
dc.language.isoen-
dc.subject.MESHAntineoplastic Agents-
dc.subject.MESHApoptosis Inducing Factor-
dc.subject.MESHCarcinoma, Hepatocellular-
dc.subject.MESHCell Line, Tumor-
dc.subject.MESHDose-Response Relationship, Drug-
dc.subject.MESHHMGB1 Protein-
dc.subject.MESHHumans-
dc.subject.MESHLiver Neoplasms-
dc.subject.MESHNAD(P)H Dehydrogenase (Quinone)-
dc.subject.MESHNaphthoquinones-
dc.subject.MESHNecrosis-
dc.subject.MESHNuclear Pore Complex Proteins-
dc.subject.MESHPoly(ADP-ribose) Polymerases-
dc.subject.MESHProtein Kinase Inhibitors-
dc.subject.MESHProtein Transport-
dc.subject.MESHRNA Interference-
dc.subject.MESHRNA-Binding Proteins-
dc.subject.MESHReactive Oxygen Species-
dc.subject.MESHReceptor-Interacting Protein Serine-Threonine Kinases-
dc.subject.MESHSignal Transduction-
dc.subject.MESHTime Factors-
dc.subject.MESHTransfection-
dc.titleβ-Lapachone induces programmed necrosis through the RIP1-PARP-AIF-dependent pathway in human hepatocellular carcinoma SK-Hep1 cells.-
dc.typeArticle-
dc.identifier.pmid24832602-
dc.identifier.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4047891/-
dc.contributor.affiliatedAuthor김, 유선-
dc.type.localJournal Papers-
dc.identifier.doi10.1038/cddis.2014.202-
dc.citation.titleCell death & disease-
dc.citation.volume5-
dc.citation.date2014-
dc.citation.startPagee1230-
dc.citation.endPagee1230-
dc.identifier.bibliographicCitationCell death & disease, 5. : e1230-e1230, 2014-
dc.identifier.eissn2041-4889-
dc.relation.journalidJ020414889-
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
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