Salinomycin Induces Autophagy in Colon and Breast Cancer Cells with Concomitant Generation of Reactive Oxygen Species 英文参考文献.docVIP

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Salinomycin Induces Autophagy in Colon and Breast Cancer Cells with Concomitant Generation of Reactive Oxygen Species 英文参考文献.doc

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Salinomycin Induces Autophagy in Colon and Breast Cancer Cells with Concomitant Generation of Reactive Oxygen Species 英文参考文献

SalinomycinInducesAutophagyinColonandBreast CancerCellswithConcomitantGenerationofReactive OxygenSpecies BerlindaVerdoodt,MarkusVogt,IngeSchmitz,Sven-ThorstenLiffers,AndreaTannapfel, AlirezaMirmohammadsadegh* InstituteofPathology,Ruhr-UniversityBochum,Bochum,Germany Abstract Background:Salinomycinisapolyetherionophoreantibioticthathasrecentlybeenshowntoinducecelldeathinhuman cancer cells displaying multiple mechanisms of drug resistance. The underlying mechanisms leading to cell death after salinomycin treatment have not been well characterized. We therefore investigated the role of salinomycin in caspase dependentand independent cell death in coloncancer (SW480,SW620, RKO) andbreast cancer celllines (MCF-7, T47D, MDA-MB-453). Methodology/PrincipalFindings:Wedetectedfeaturesofapoptosisinallcelllinestested,buttheexecutorcaspases3and 7 were only strongly activated in RKO and MDA-MB-453 cells. MCF-7 and SW620 cells instead presented features of autophagysuchascytoplasmicvacuolizationandLC3processing.Caspaseproficientcelllinesactivatedautophagyatlower salinomycinconcentrationsandbeforetheonsetofcaspaseactivation.Salinomycinalsoledtotheformationofreactive oxygenspecies(ROS)elicitingJNKactivationandinductionofthetranscriptionfactorJUN.Salinomycinmediatedcelldeath couldbepartiallyinhibitedbythefreeradicalscavengerN-acetyl-cysteine,implicatingROSformationinthemechanismof salinomycintoxicity. Conclusions:Ourdataindicatethat,inadditiontoitspreviouslyreportedinductionofcaspasedependentapoptosis,the initiationofautophagyisanimportantandearlyeffectofsalinomycinintumorcells. Citation:VerdoodtB,VogtM,SchmitzI,LiffersS-T,TannapfelA,etal.(2012)SalinomycinInducesAutophagyinColonandBreastCancerCellswithConcomitant GenerationofReactiveOxygenSpecies.PLoSONE7(9):e44132.doi:10.1371/journal.pone.0044132 Editor:HiroyasuNakano,JuntendoUniversitySchoolofMedicine,Japan ReceivedFebruary29,2012;AcceptedJuly31,2012;PublishedSeptember19,2012 Copyright: ? 2012 Verdoodt et al. This is an open-acce