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Induction of cytosine arabinoside-resistant human myeloid leukemia cell death through autophagy regulation by hydroxychloroquine

DC FieldValueLanguage
dc.contributor.author김영삼-
dc.contributor.author김윤덕-
dc.contributor.author김진석-
dc.contributor.author민유홍-
dc.contributor.author장지은-
dc.contributor.author정준원-
dc.date.accessioned2016-02-04T11:48:53Z-
dc.date.available2016-02-04T11:48:53Z-
dc.date.issued2015-
dc.identifier.issn0753-3322-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/141263-
dc.description.abstractWe investigated the effects of the autophagy inhibitor hydroxychloroquine (HCQ) on cell death of cytosine arabinoside (Ara-C)-resistant human acute myeloid leukemia (AML) cells. Ara-C-sensitive (U937, AML-2) and Ara-C-resistant (U937/AR, AML-2/AR) human AML cell lines were used to evaluate HCQ-regulated cytotoxicity, autophagy, and apoptosis as well as effects on cell death-related signaling pathways. We found that HCQ-induced dose- and time-dependent cell death in Ara-C-resistant cells compared to Ara-C-sensitive cell lines. The extent of cell death and features of HCQ-induced autophagic markers including increase in microtubule-associated protein light chain 3 (LC3) I conversion to LC3-II, beclin-1, ATG5, as well as green fluorescent protein-LC3 positive puncta and autophagosome were remarkably greater in U937/AR cells. Also, p62/SQSTM1 was increased in response to HCQ. p62/SQSTM1 protein interacts with both LC3-II and ubiquitin protein and is degraded in autophagosomes. Therefore, a reduction of p62/SQSTM1 indicates increased autophagic degradation, whereas an increase of p62/SQSTM1 by HCQ indicates inhibited autophagic degradation. Knock down of p62/SQSTM1 using siRNA were prevented the HCQ-induced LC3-II protein level as well as significantly reduced the HCQ-induced cell death in U937/AR cells. Also, apoptotic cell death and caspase activation in U937/AR cells were increased by HCQ, provided evidence that HCQ-induced autophagy blockade. Taken together, our data show that HCQ-induced apoptotic cell death in Ara-C-resistant AML cells through autophagy regulation.-
dc.description.statementOfResponsibilityopen-
dc.format.extent87~96-
dc.relation.isPartOfBIOMEDICINE & PHARMACOTHERAPY-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAntimetabolites, Antineoplastic/pharmacology-
dc.subject.MESHAntimetabolites, Antineoplastic/therapeutic use-
dc.subject.MESHAutophagy/drug effects*-
dc.subject.MESHAutophagy/physiology-
dc.subject.MESHCell Death/drug effects-
dc.subject.MESHCell Death/physiology-
dc.subject.MESHCytarabine/pharmacology-
dc.subject.MESHCytarabine/therapeutic use-
dc.subject.MESHDrug Resistance, Neoplasm/drug effects*-
dc.subject.MESHDrug Resistance, Neoplasm/physiology-
dc.subject.MESHHumans-
dc.subject.MESHHydroxychloroquine/pharmacology*-
dc.subject.MESHHydroxychloroquine/therapeutic use-
dc.subject.MESHLeukemia, Myeloid, Acute/drug therapy-
dc.subject.MESHLeukemia, Myeloid, Acute/pathology*-
dc.subject.MESHU937 Cells-
dc.titleInduction of cytosine arabinoside-resistant human myeloid leukemia cell death through autophagy regulation by hydroxychloroquine-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Internal Medicine (내과학)-
dc.contributor.googleauthorYundeok Kim-
dc.contributor.googleauthorJu-In Eom-
dc.contributor.googleauthorHoi-Kyung Jeung-
dc.contributor.googleauthorJi Eun Jang-
dc.contributor.googleauthorJin Seok Kim-
dc.contributor.googleauthorJune-Won Cheong-
dc.contributor.googleauthorYoung Sam Kim-
dc.contributor.googleauthorYoo Hong Min-
dc.identifier.doi10.1016/j.biopha.2015.05.012-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA00707-
dc.contributor.localIdA00790-
dc.contributor.localIdA01017-
dc.contributor.localIdA01407-
dc.contributor.localIdA03477-
dc.contributor.localIdA03729-
dc.relation.journalcodeJ00322-
dc.identifier.eissn1950-6007-
dc.identifier.pmid26211587-
dc.identifier.urlhttp://www.sciencedirect.com/science/article/pii/S0753332215001250-
dc.subject.keywordAcute myeloid leukemia-
dc.subject.keywordApoptosis-
dc.subject.keywordAutophagy-
dc.subject.keywordChemoresistance-
dc.subject.keywordHydroxychloroquine-
dc.contributor.alternativeNameKim, Young Sam-
dc.contributor.alternativeNameKim, Yun Deok-
dc.contributor.alternativeNameKim, Jin Seok-
dc.contributor.alternativeNameMin, Yoo Hong-
dc.contributor.alternativeNameJang, Ji Eun-
dc.contributor.alternativeNameCheong, June Won-
dc.contributor.affiliatedAuthorKim, Young Sam-
dc.contributor.affiliatedAuthorKim, Yun Deok-
dc.contributor.affiliatedAuthorKim, Jin Seok-
dc.contributor.affiliatedAuthorMin, Yoo Hong-
dc.contributor.affiliatedAuthorJang, Ji Eun-
dc.contributor.affiliatedAuthorCheong, June-Won-
dc.rights.accessRightsnot free-
dc.citation.volume73-
dc.citation.startPage87-
dc.citation.endPage96-
dc.identifier.bibliographicCitationBIOMEDICINE & PHARMACOTHERAPY, Vol.73 : 87-96, 2015-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers

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