Resveratrol Induces Growth Arrest and Apoptosis through Activation of FOXO Transcription Factors in Prostate Cancer Cells 英文参考文献.docVIP

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Resveratrol Induces Growth Arrest and Apoptosis through Activation of FOXO Transcription Factors in Prostate Cancer Cells 英文参考文献.doc

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Resveratrol Induces Growth Arrest and Apoptosis through Activation of FOXO Transcription Factors in Prostate Cancer Cells 英文参考文献

ResveratrolInducesGrowthArrestandApoptosis throughActivationofFOXOTranscriptionFactorsin ProstateCancerCells QingheChen1,SuthakarGanapathy2,KaranP.Singh3,SharmilaShankar4,RakeshK.Srivastava5* 1Virginia Bioinformatics Institute, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, United States of America, 2Division of Radiation Biology, Department of Radiation Oncology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America, 3Department of Biostatistics, University of North Texas Health Science Center at Fort Worth, Fort Worth, Texas, United States of America, 4Department of Pathology and Laboratory Medicine,TheUniversityofKansasCancerCenter,TheUniversityofKansasMedicalCenter,KansasCity,Kansas,UnitedStatesofAmerica,5DepartmentofPharmacology, ToxicologyandTherapeutics,andMedicine,TheUniversityofKansasCancerCenter,TheUniversityofKansasMedicalCenter,KansasCity,Kansas,UnitedStatesofAmerica Abstract Background:Resveratrol,anaturallyoccurringphytopolyphenolcompound,hasattractedextensiveinterestinrecentyears becauseofitsdiversepharmacologicalcharacteristics.Althoughresveratrolpossesseschemopreventivepropertiesagainst severalcancers,themolecularmechanismsbywhichitinhibitscellgrowthandinducesapoptosishavenotbeenclearly understood.ThepresentstudywascarriedouttoexaminewhetherPI3K/AKT/FOXOpathwaymediatesthebiologicaleffects ofresveratrol. Methodology/Principal Findings: Resveratrol inhibited the phosphorylation of PI3K, AKT and mTOR. Resveratrol, PI3K inhibitors(LY294002andWortmannin)andAKTinhibitoraloneslightlyinducedapoptosisinLNCaPcells.Theseinhibitors further enhanced the apoptosis-inducing potential of resveratrol. Overexpression of wild-type PTEN slightly induced apoptosis.WildtypePTENandPTEN-G129Eenhancedresveratrol-inducedapoptosis,whereasPTEN-G129Rhadnoeffecton proapoptotic effects of resveratrol. Furthermore, apoptosis-inducing potential of resveratrol was enhanced by dominant negativeAKT,andi