Grape Proanthocyanidin Inhibit Pancreatic Cancer Cell Growth In Vitro and In Vivo through Induction of Apoptosis and by Targeting the PI3KAkt Pathway 英文参考文献.docVIP
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Grape Proanthocyanidin Inhibit Pancreatic Cancer Cell Growth In Vitro and In Vivo through Induction of Apoptosis and by Targeting the PI3KAkt Pathway 英文参考文献
GrapeProanthocyanidinInhibitPancreaticCancerCell
GrowthInVitroandInVivothroughInductionof
ApoptosisandbyTargetingthePI3K/AktPathway
RamPrasad2,MuditVaid2,SantoshK.Katiyar1,2,3,4*
1Birmingham VeteransAffairsMedicalCenter,Birmingham,Alabama,UnitedStatesofAmerica, 2DepartmentofDermatology,UniversityofAlabamaatBirmingham,
Birmingham, Alabama, United States of America, 3Nutrition Obesity Research Center, University of Alabama at Birmingham, Birmingham, Alabama, United States of
America,4ComprehensiveCancerCenter,UniversityofAlabamaatBirmingham,Birmingham,Alabama,UnitedStatesofAmerica
Abstract
Pancreaticcancerisanaggressivemalignancythatisfrequentlydiagnosedatanadvancedstagewithpoorprognosis.Here,
wereportthechemotherapeuticeffectsofbioactiveproanthocyanidinsfromgrapeseeds(GSPs)asassessedusingInVitro
andInVivomodels.Treatmentofhumanpancreaticcancercells(Miapaca-2,PANC-1andAsPC-1)withGSPsInVitroreduced
cell viability and increased G2/M phase arrest of the cell cycle leading to induction of apoptosis in a dose- and time-
dependentmanner.TheGSPs-inducedapoptosisofpancreaticcancercellswasassociatedwithadecreaseinthelevelsof
Bcl-2andBcl-xlandanincreaseinthelevelsofBaxandactivatedcaspase-3.TreatmentofMiapaca-2andPANC-1cellswith
GSPs also decreased the levels of phosphatidylinositol-3-kinase (PI3K) and phosphorylation of Akt at ser473 . siRNA
knockdownofPI3KfrompancreaticcancercellsalsoreducedthephosphorylationofAkt.Further,dietaryadministrationof
GSPs(0.5%,w/w)asasupplementedAIN76AcontroldietsignificantlyinhibitedthegrowthofMiapaca-2pancreatictumor
xenograftsgrownsubcutaneouslyinathymicnudemice,whichwasassociatedwith:(i)inhibitionofcellproliferation,(ii)
inductionofapoptosisoftumorcells,(iii)increasedexpressionofBax,reducedexpressionofanti-apoptoticproteinsand
activationofcaspase-3-positivecells,and(iv)decreasedexpressionofPI3Kandp-Aktintumorxenografttissues.Together,
theseresultssuggestthatGSPsmayhaveapotentialchemotherapeuticeffectonpancreaticcancercellgrowth.
Citation
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