ProductDescription
CucurbitacinB(CuB)belongstoaclassofhighlyoxidizedtetracyclictriterpenoids;couldrepresscancercellprogression.IC50value:Target:anticancernaturalcompoundinvitro:Cucurbitacin-Binhibitedgrowthandmodulatedexpressionofcell-cycleregulatorsinSHSY5Ycells.Atthemolecularlevel,wefoundthatCucurbitacin-BinhibitedAKTsignalingactivationthroughup-regulationofPTEN.CuBinducedapoptosisofA549cellsina-concentration-dependentmanner,asdeterminedbyfluorescencemicroscopy,flowcytometryandtransmissionelectronmicroscopy.CuBdose-dependentlyinhibitedlungcancercellproliferation,withcellcycleinhibitionandcyclinB1downregulation.ApoptosisinducedbyCuBwasshowntobeassociatedwithcytochromecrelease,B-celllymphoma2downregulationandsignaltransducerandactivatoroftranscription3pathwayinhibition.CuBinhibitedITGA6andITGB4(integrin伪6andintegrin尾4),whichareoverexpressedinbreastcancer.FurThermore,CuBalsoinducedtheexpressionofmajorITGB1andITGB3,whichareknowntocauseintegrin-mediatedcelldeath.CucBtreatmentcausedDNAdouble-strandbreaks(DSBs)withoutaffectingthesignaltransducerandactivatoroftranscription3(STAT3),thepotentialmoleculartargetforCucB.CucBtriggersATM-activatedChk1-Cdc25C-Cdk1,whichcouldbereversedbybothATMsiRNAandChk1siRNA.CucBalsotriggersATM-activatedp53-14-3-3-蟽pathways,whichcouldbereversedbyATMsiRNA.invivo:EfficacyofCuBwastestedinvivousingtwodifferentorthotopicmodelsofbreastcancer.MDA-MB-231and4T-1cellswereinjectedorthotopicallyinthemammaryfatpadoffemaleathymicnudemiceorBALB/cmicerespectively.OurresultsshowedthatCuBadmiNISTrationinhibitedMDA-MB-231orthotopictumorsby55%,and4T-1tumorsby40%.The4T-1cellsrepresentstageIVbreastcancerandformveryaggressivetumors.
