Bullatacin Triggered ABCB1-Overexpressing Cell Apoptosis via the Mitochondrial-Dependent Pathway英文文献资料.docVIP

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Bullatacin Triggered ABCB1-Overexpressing Cell Apoptosis via the Mitochondrial-Dependent Pathway英文文献资料.doc

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Bullatacin Triggered ABCB1-Overexpressing Cell Apoptosis via the Mitochondrial-Dependent Pathway英文文献资料

HindawiPublishingCorporation JournalofBiomedicineandBiotechnology Volume2009,ArticleID867123,9pages doi:10.1155/2009/867123 ResearchArticle BullatacinTriggeredABCB1-OverexpressingCellApoptosisvia theMitochondrial-DependentPathway Yong-JuLiang,XuZhang,Chun-LingDai,Jian-YeZhang,Yan-YanYan,Mu-ShengZeng, Li-MingChen,andLi-WuFu StateKeyLaboratoryofOncologyinSouthChina,CancerCenter,SunYat-SenUniversity,Guangzhou510060,China CorrespondenceshouldbeaddressedtoLi-WuFu,fulw@mail.sysu.edu.cn Received20February2009;Accepted11May2009 RecommendedbyDominicFan Thispaperwastoexplorebullatacin-mediatedmultidrug-resistantcellapoptosisatextremelylowconcentration.Toinvestigate itsprecisemechanisms,thepathwayofcellapoptosisinducedbybullatacinwasexamined.Bullatacincausesanupregulation ofROSandadownregulationofΔΨminaconcentration-dependentmannerinABCB1-overexpressingKBv200cells.Inaddition, cleaversofcaspase-9,caspase-3,andPARPwereobservedfollowingthereleaseofcytochromecfrommitochondriaafterbullatacin treatment.However,neithercleavageofcaspase-8norchangeofexpressionlevelofbcl-2,baxandFaswasobservedbythesame treatment.PretreatingKBv200cellswithN-acetylcysteine,anantioxidantmodulator,resultedinasigni?cantreductionofROS generationandcellapoptosisinducedbybullatacin.Bullatacin-inducedapoptosiswasantagonizedbyz-LEHD-fmk,acaspase-9 inhibitor,butnotbyz-IETD-fmk,acaspase-8inhibitor.TheseimpliedthatapoptosisofKBv200cellsinducedbybullatacinwas associatedwiththemitochondria-dependentpathwaythatwaslimitedtoactivationofapicalcaspase-9. Copyright?2009Yong-JuLiangetal.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttributionLicense, whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited. 1.Introduction via(i)removingthetoxinsfromthecelland(ii)inhibiting the activation of caspases-8 and -3 but not caspase-9. So it has been postulated that MDR cells were sensitive to apoptosisinducedbyamitochondria-dependentpathway. Up to today, strategies ai