Brazilian Propolis Suppresses Angiogenesis by Inducing Apoptosis in Tube-Forming Endothelial Cells through Inactivation of Survival Signal ERK12英文文献资料.docVIP

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Brazilian Propolis Suppresses Angiogenesis by Inducing Apoptosis in Tube-Forming Endothelial Cells through Inactivation of Survival Signal ERK12英文文献资料.doc

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Brazilian Propolis Suppresses Angiogenesis by Inducing Apoptosis in Tube-Forming Endothelial Cells through Inactivation of Survival Signal ERK12英文文献资料

HindawiPublishingCorporation Evidence-BasedComplementaryandAlternativeMedicine Volume2011,ArticleID870753,8pages doi:10.1093/ecam/nep024 OriginalArticle BrazilianPropolisSuppressesAngiogenesisby InducingApoptosisinTube-FormingEndothelialCellsthrough InactivationofSurvivalSignalERK1/2 KazuhiroKunimasa, ShigenoriKumazawa, KazuhikoKaji, andToshiroOhta 1 Mok-RyeonAhn,1,2TomomiKobayashi, 1 RyojiEguchi, TsutomuNakayama, 1 3 1 YoshihiroFujimori, 4 TakashiNakano, 3 1 1 1 GraduateSchoolofNutritionalandEnvironmentalSciencesandGlobalCOEProgram,UniversityofShizuoka, Shizuoka422-8526,Japan 2 3 4 DepartmentofFoodandNutrition,Dong-AUniversity,840Hadan-2dong,Saha-gu,Busan604-714,RepublicofKorea DepartmentofThoracicOncology,HyogoCollegeofMedicine,Japan CancerCenter,HyogoCollegeofMedicine,Hyogo663-8501,Japan CorrespondenceshouldbeaddressedtoToshiroOhta,ohtat@u-shizuoka-ken.ac.jp Received8October2008;Accepted3March2009 Copyright?2011KazuhiroKunimasaetal.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttribution License,whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperly cited. We recently reported that propolis suppresses tumor-induced angiogenesis through tube formation inhibition and apoptosis inductioninendothelialcells.However,molecularmechanismsunderlyingsuchangiogenesissuppressionbypropolishavenot beenfullyelucidated.Theaimofthisstudywastoinvestigatethee?ectsofethanolextractofBrazilianpropolis(EEBP)ontwo majorsurvivalsignals,extracellularsignal-regulatedkinase1/2(ERK1/2)andAkt,andtoelucidatewhetherchangesinthesesignals wereactuallyinvolved inantiangiogenic e?ects ofthepropolis. Detection bywestern blottingrevealed thatEEBPsuppressed phosphorylationofERK1/2,butnotthatofAkt.PharmacologicalinhibitionbyU0126demonstratedthatERK1/2inactivation alonewasenoughtoinhibittubeformationandinduceapoptosis.ItwasalsoshownthatEEBPandU0126similarlyinduced activationofcaspase-3andcleavageofpolyADP-ribosepolymerase(PARP)andlaminA/C,al