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Carbonyl reductase 1 offers a novel therapeutic target to enhance leukemia treatment by arsenic trioxide.

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dc.contributor.author민유홍-
dc.date.accessioned2014-12-19T16:37:09Z-
dc.date.available2014-12-19T16:37:09Z-
dc.date.issued2012-
dc.identifier.issn0008-5472-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/89870-
dc.description.abstractArsenic trioxide (As2O3) is used, in current practice, as an effective chemotherapeutic agent for acute promyelocytic leukemia (APL). However, the side effects and relatively low efficacy of As2O3 in treating other leukemias have limited its wider use in therapeutic applications. In the present study, we found that the expression of carbonyl reductase 1 (CBR1) affects the resistance to As2O3 in leukemias, including APL; As2O3 upregulated CBR1 expression at the transcriptional level by stimulating the activity of the transcription factor activator protein-1. Moreover, CBR1 overexpression was sufficient to protect cells against As2O3 through modulation of the generation of reactive oxygen species, whereas the attenuation of CBR1 was sufficient to sensitize cells to As2O3. A combination treatment with the specific CBR1 inhibitor hydroxy-PP-Me remarkably increased As2O3-induced apoptotic cell death compared with As2O3 alone, both in vitro and in vivo. These results were confirmed in primary cultured human acute and chronic myeloid leukemia cells, with no significant cell death observed in normal leukocytes. Taken together, our findings indicate that CBR1 contributes to the low efficacy of As2O3 and, therefore, is a rational target for the development of combination chemotherapy with As2O3 in diverse leukemias including APL.-
dc.description.statementOfResponsibilityopen-
dc.relation.isPartOfCANCER RESEARCH-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAlcohol Oxidoreductases/antagonists & inhibitors*-
dc.subject.MESHAlcohol Oxidoreductases/biosynthesis-
dc.subject.MESHAlcohol Oxidoreductases/genetics-
dc.subject.MESHAlcohol Oxidoreductases/metabolism*-
dc.subject.MESHAnimals-
dc.subject.MESHAntineoplastic Combined Chemotherapy Protocols/pharmacology*-
dc.subject.MESHApoptosis/drug effects-
dc.subject.MESHArsenicals/administration & dosage-
dc.subject.MESHArsenicals/pharmacology*-
dc.subject.MESHDrug Synergism-
dc.subject.MESHEnzyme Activation/drug effects-
dc.subject.MESHEnzyme Inhibitors/administration & dosage-
dc.subject.MESHEnzyme Inhibitors/pharmacology*-
dc.subject.MESHFemale-
dc.subject.MESHGene Knockdown Techniques-
dc.subject.MESHHL-60 Cells-
dc.subject.MESHHumans-
dc.subject.MESHK562 Cells-
dc.subject.MESHLeukemia, Myeloid/drug therapy*-
dc.subject.MESHLeukemia, Myeloid/enzymology*-
dc.subject.MESHLeukemia, Myeloid/genetics-
dc.subject.MESHLeukemia, Myeloid/pathology-
dc.subject.MESHMice-
dc.subject.MESHMice, Inbred BALB C-
dc.subject.MESHNADPH Oxidases/metabolism-
dc.subject.MESHOxides/administration & dosage-
dc.subject.MESHOxides/pharmacology*-
dc.subject.MESHPromoter Regions, Genetic-
dc.subject.MESHReactive Oxygen Species/metabolism-
dc.subject.MESHTranscription Factor AP-1/metabolism-
dc.subject.MESHU937 Cells-
dc.subject.MESHUp-Regulation/drug effects-
dc.subject.MESHXenograft Model Antitumor Assays-
dc.titleCarbonyl reductase 1 offers a novel therapeutic target to enhance leukemia treatment by arsenic trioxide.-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Internal Medicine (내과학)-
dc.contributor.googleauthorMiran Jang-
dc.contributor.googleauthorYeonghwan Kim-
dc.contributor.googleauthorHyeran Won-
dc.contributor.googleauthorSangbin Lim-
dc.contributor.googleauthorJyothi K.R-
dc.contributor.googleauthorAmarjargal Dashdorj-
dc.contributor.googleauthorYoo Hong Min-
dc.contributor.googleauthorSi-Young Kim-
dc.contributor.googleauthorKevan M. Shokat-
dc.contributor.googleauthorJoohun Ha-
dc.contributor.googleauthorSung Soo Kim-
dc.identifier.doi22719067-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA01407-
dc.relation.journalcodeJ00452-
dc.identifier.eissn1538-7445-
dc.identifier.pmid22719067-
dc.identifier.urlhttp://cancerres.aacrjournals.org/content/72/16/4214-
dc.subject.keywordAlcohol Oxidoreductases/antagonists & inhibitors*-
dc.subject.keywordAlcohol Oxidoreductases/biosynthesis-
dc.subject.keywordAlcohol Oxidoreductases/genetics-
dc.subject.keywordAlcohol Oxidoreductases/metabolism*-
dc.subject.keywordAnimals-
dc.subject.keywordAntineoplastic Combined Chemotherapy Protocols/pharmacology*-
dc.subject.keywordApoptosis/drug effects-
dc.subject.keywordArsenicals/administration & dosage-
dc.subject.keywordArsenicals/pharmacology*-
dc.subject.keywordDrug Synergism-
dc.subject.keywordEnzyme Activation/drug effects-
dc.subject.keywordEnzyme Inhibitors/administration & dosage-
dc.subject.keywordEnzyme Inhibitors/pharmacology*-
dc.subject.keywordFemale-
dc.subject.keywordGene Knockdown Techniques-
dc.subject.keywordHL-60 Cells-
dc.subject.keywordHumans-
dc.subject.keywordK562 Cells-
dc.subject.keywordLeukemia, Myeloid/drug therapy*-
dc.subject.keywordLeukemia, Myeloid/enzymology*-
dc.subject.keywordLeukemia, Myeloid/genetics-
dc.subject.keywordLeukemia, Myeloid/pathology-
dc.subject.keywordMice-
dc.subject.keywordMice, Inbred BALB C-
dc.subject.keywordNADPH Oxidases/metabolism-
dc.subject.keywordOxides/administration & dosage-
dc.subject.keywordOxides/pharmacology*-
dc.subject.keywordPromoter Regions, Genetic-
dc.subject.keywordReactive Oxygen Species/metabolism-
dc.subject.keywordTranscription Factor AP-1/metabolism-
dc.subject.keywordU937 Cells-
dc.subject.keywordUp-Regulation/drug effects-
dc.subject.keywordXenograft Model Antitumor Assays-
dc.contributor.alternativeNameMin, Yoo Hong-
dc.contributor.affiliatedAuthorMin, Yoo Hong-
dc.citation.volume72-
dc.citation.number16-
dc.citation.startPage4214-
dc.citation.endPage4224-
dc.identifier.bibliographicCitationCANCER RESEARCH, Vol.72(16) : 4214-4224, 2012-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers

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