Cell-Type-Specific Effects of Silibinin on Vitamin D-Induced Differentiation of Acute Myeloid Leukemia Cells Are Associated with Differential Modulation of RXRα Levels英文文献资料.docVIP

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Cell-Type-Specific Effects of Silibinin on Vitamin D-Induced Differentiation of Acute Myeloid Leukemia Cells Are Associated with Differential Modulation of RXRα Levels英文文献资料.doc

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Cell-Type-Specific Effects of Silibinin on Vitamin D-Induced Differentiation of Acute Myeloid Leukemia Cells Are Associated with Differential Modulation of RXRα Levels英文文献资料

HindawiPublishingCorporation LeukemiaResearchandTreatment Volume2012,ArticleID401784,12pages doi:10.1155/2012/401784 ResearchArticle Cell-Type-Speci?cEffectsofSilibininonVitaminD-Induced DifferentiationofAcuteMyeloidLeukemiaCellsAreAssociated withDifferentialModulationofRXRαLevels RinaWassermann,VictoriaNovik,andMichaelDanilenko DepartmentofClinicalBiochemistry,FacultyofHealthSciences,Ben-GurionUniversityoftheNegev,P.O.Box653, 84105Beer-Sheva,Israel CorrespondenceshouldbeaddressedtoMichaelDanilenko,misha@bgu.ac.il Received26February2012;Accepted15March2012 AcademicEditor:GeorgeP.Studzinski Copyright?2012RinaWassermannetal. This is an open access article distributed under the Creative Commons Attribution License,whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperly cited. Plantpolyphenolshavebeenshowntoenhancethedi?erentiationofacutemyeloidleukemia(AML)cellsinducedbythehormonal formofvitaminD3(1α,25-dihydroxyvitaminD3;1,25D).However,howtheseagentsmodulate1,25De?ectsindi?erentsubtypes ofAMLcellsremainspoorlyunderstood.Here,weshowthatbothcarnosicacid(CA)andsilibinin(SIL)synergisticallyenhancd 1,25D-induceddi?erentiationofmyeloblasticHL60cells.However,inpromonocyticU937cells,onlyCAcausedpotentiation whileSILattenuated1,25De?ect.Theenhancede?ectof1,25D+CAwasaccompaniedbyincreasesinboththevitaminDreceptor (VDR)andretinoidXreceptoralpha(RXRα)proteinlevelsandvitaminDresponseelement(VDRE)transactivationinboth celllines.SimilarincreaseswereobservedinHL60cellstreatedwith1,25D+SIL.InU937cells,however,SILinhibited1,25D- inducedVDREtransactivationconcomitantwithdownregulationofRXRαatbothtranscriptionalandposttranscriptionallevels. Theseinhibitorye?ectscorrelatedwith theinabilityofSIL,with orwithout1,25D,toactivatetheNrf2/antioxidantresponse elementsignalingpathwayinU937cells.Theseresultssuggestthatoppositee?ectsofSILon1,25D-induceddi?erentiationof HL60andU937cellsmaybedeterminedbycell-type-speci?csignalingandtranscriptionalr