Englerin A Selectively Induces Necrosis in Human Renal Cancer Cells 英文参考文献.docVIP

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Englerin A Selectively Induces Necrosis in Human Renal Cancer Cells 英文参考文献.doc

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Englerin A Selectively Induces Necrosis in Human Renal Cancer Cells 英文参考文献

EnglerinASelectivelyInducesNecrosisinHumanRenal CancerCells FlorianJ.Sulzmaier1,3,ZhenwuLi2,MikaL.Nakashige2,DavidM.Fash2,WilliamJ.Chain1,2, JoeW.Ramos1,3 * 1CancerBiologyProgram,UniversityofHawaiiCancerCenter,UniversityofHawaiiatManoa,Honolulu,Hawaii,UnitedStatesofAmerica,2DepartmentofChemistry, UniversityofHawaiiatManoa,Honolulu,Hawaii,UnitedStatesofAmerica,3DepartmentofMolecularBiosciencesandBioengineering,UniversityofHawaiiatManoa, Honolulu,Hawaii,UnitedStatesofAmerica Abstract The numberof renalcancers has increased overthelast tenyears andpatient survival inadvanced stages remains very poor. Therefore, new therapeutic approaches for renal cancer are essential. Englerin A is a natural product with a very potent and selective cytotoxicity against renal cancer cells. This makes it a promising drug candidate that may improve currenttreatmentstandardsforpatientswithrenalcancersinallstages.However,littleisknownaboutenglerinA’smodeof actionintargetingspecificallyrenalcancercells.OurstudyisthefirsttoinvestigatethebiologicalmechanismofenglerinA actionindetail.WereportthatenglerinAisspecificforrenaltumorcellsanddoesnotaffectnormalkidneycells.Wefind thatenglerinAtreatmentinducesnecroticcelldeathinrenalcancercellsbutnotinnormalkidneycells.Wefurthershow that autophagic and pyroptotic proteins are unaffected by the compound and that necrotic signaling in these cells coincidedwithproductionofreactiveoxygenspeciesandcalciuminfluxintothecytoplasm.Asthefirststudytoanalyzethe biologicaleffectsofenglerinA,ourworkprovidesanimportantbasisfortheevaluationandvalidationofthecompound’s useasananti-tumordrug.ItalsoprovidesacontextinwhichtoidentifythespecifictargetortargetsofenglerinAinrenal cancercells. Citation:SulzmaierFJ,LiZ,NakashigeML,FashDM,ChainWJ,etal.(2012)EnglerinASelectivelyInducesNecrosisinHumanRenalCancerCells.PLoSONE7(10): e48032.doi:10.1371/journal.pone.0048032 Editor:KalpanaGhoshal,TheOhioStateUniversity,UnitedStatesofAmerica ReceivedJuly6,2012;AcceptedSeptember26,2012