Organometallic Iron(III)-Salophene Exerts Cytotoxic Properties in Neuroblastoma Cells via MAPK Activation and ROS Generation 英文参考文献.docVIP

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Organometallic Iron(III)-Salophene Exerts Cytotoxic Properties in Neuroblastoma Cells via MAPK Activation and ROS Generation 英文参考文献.doc

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Organometallic Iron(III)-Salophene Exerts Cytotoxic Properties in Neuroblastoma Cells via MAPK Activation and ROS Generation 英文参考文献

OrganometallicIron(III)-SalopheneExertsCytotoxic PropertiesinNeuroblastomaCellsviaMAPKActivation andROSGeneration KyuKwangKim1*,RakeshK.Singh1,RobertM.Strongin2,RichardG.Moore1,LaurentBrard3,ThiloS. Lange1,4 * 1MolecularTherapeuticsLaboratory,PrograminWomen’sOncology,DepartmentofObstetricsandGynecology,WomenandInfants’Hospital,AlpertMedicalSchool, BrownUniversity,Providence,RhodeIsland,UnitedStatesofAmerica,2DepartmentofChemistry,PortlandStateUniversity,Portland,Oregon,UnitedStatesofAmerica, 3Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Southern Illinois University School of Medicine, Springfield, Illinois, United States of America,4DepartmentofMolecularBiology,CellBiology,andBiochemistry,BrownUniversity,Providence,RhodeIsland,UnitedStatesofAmerica Abstract The objective of the present study was to investigate the specific effects of Iron(III)-salophene (Fe-SP) on viability, morphology,proliferation,cellcycleprogression,ROSgenerationandpro-apoptoticMAPKactivationinneuroblastoma(NB) cells.ANCI-DTPcancerscreenrevealedthatFe-SPdisplayedhightoxicityagainstcelllinesofdifferenttumororiginbutnot tumor type-specificity. In a viability screen Fe-SP exhibited high cytotoxicity against all three NB cell lines tested. The compoundcausedcellcyclearrestinG1phase,suppressionofcellsprogressingthroughSphase,morphologicalchanges, disruptionofthemitochondrialmembranedepolarizationpotential,inductionofapoptoticmarkersaswellasp38andJNK MAPK activation, DNA degradation, and elevated generation of reactive oxygen species (ROS) in SMS-KCNR NB cells. In contrasttoFe-SP,non-complexedsalopheneorCu(II)-SPdidnotraiseROSlevelsinNBorSKOV-3ovariancancercontrol cells.CytotoxicityofFe-SPandactivationofcaspase-3,-7,PARP,pro-apoptoticp38andJNKMAPKcouldbepreventedby co-treatmentwithantioxidantssuggestingROSgenerationistheprimarymechanismofcytotoxicaction.Wereporthere thatFe-SPisapotentgrowth-suppressingandcytotoxicagentfor invitroNBcelllinesand,duetoitshightolerance