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简介：Theadaptivetreatmenttolerance(ATT)ofcancercellsisthemainencumbrancetocancerchemotherapy.Apotentialsolutiontothisproblemistotreatcancercellswithmultipledrugsusingnanoparticles(NPs).Inthisstudy,wetestedtheco-administrationofcurcumin(Cur)anddoxorubicin(Dox)toMCF-7resistantbreastcancercellstoblocktheATTandelicitefficientcellkilling.Drugswereco-administeredtocellsbothsequentiallyandsimultaneously.Sequentialdrugco-administrationwascarriedoutbypre-treatingthecellswithalbuminnanoparticles(ANPs)loadedw让hCur(Cur@ANPs)followedbytreatmentwithDox-loadedANPs(Dox@ANPs).Simultaneousdrugco-administrationwascarriedoutbytreatingthecellswithANPsloadedwithboththedrugs(Cur/Dox@ANPs).Wefoundthatthesimultaneousdrugco-administrationledtoagreaterintra-cellularaccumulationofDoxandcellkillingwithrespecttothesequentialdrugco-administration.However;thesimultaneousdrugco-administrationledtoalowerintracellularaccumulationofCurwithrespecttothesequentialdrugco-administration.WeshowedthatthisresultwasduetotheaggregationandentrapmentofCurinthelysosomesassoonasitwasreleasedfromCur@ANPs,aphenomenoncalledlysosomotropism.Incontrast,thesimultaneousreleaseofDoxandCurfromCur/Dox@ANPsintothelysosomesledtolysosomalpHelevation,which,inturn,avoidedCuraggregation,ledtolysosomeswellinganddrugreleaseinthecytosol,andfinallyprovokedefficientcellkilling.Ourstudyshedthelightonthemolecularprocessesdrivingthetherapeuticeffectsofanti-cancerdrugsco-administeredtocancercellsindifferentmanners.

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简介：Severalstudieshavedemonstratedthattheamountofbeta-amyloid(Aβ)proteininthebraincanbeloweredbydown-regulatingAβproduction,promotingAβdegradation,reducingAβoligomerizationordeposition,therebyalleviatingsymptomsofAlzheimer'sdisease.Curcuminhasbeenknowntobeaperoxisomeproliferatoractivatedreceptorgamma(PPARγ)agonistandcanobviouslyinhibitAβproductionandoligomerization.Thisstudyinvestigatedtheeffectsofcurcuminontheβ-siteAPPcleavingenzyme1(BACE1)activityandPPARγexpressioninhumanneuroblastomaSH-SY5Ycells,andvalidatedtheinhibitoryeffectsofcurcuminonAβ40/42expressioninthebrain.ResultsrevealedthatPPARγmRNAandproteinexpressioninthehumanneuroblastomaSH-SY5Ycellssignificantlyincreasedwithincreasingcurcuminconcentrationandtimecourse(P<0.05);BACE1mRNAandproteinexpressionandAβ40/42productionsignificantlydecreasedwithincreasingcurcuminconcentrationandtimecourse(P<0.05).ThechangesinPPARγandBACE1expressionduringAβproductioncouldbereversedbythePPARγantagonistGW9662.ThesefindingsindicatethatcurcuminreducedAβproductionbyactivatingPPARγexpressionandinhibitingBACE1expressioninaconcentration-andtime-dependentmanner.

简介：目的研究生长抑制因子4（ING4）在脑胶质瘤中的表达和姜黄素（curcumin）对脑胶质瘤的治疗作用,揭示curcumin抗脑胶质瘤作用的分子机制。方法体外培养U251胶质瘤细胞并以不同浓度curcumin处理细胞;以药物敏感试验和流式细胞仪分别检测curcumin对胶质瘤细胞生长和细胞周期的影响,以DNA梯度凝胶电泳检测细胞凋亡,以Westernblot分析curcumin处理后蛋白表达变化。结果ING4蛋白在正常神经细胞中高表达,在U251细胞中几乎不表达。低剂量curcumin对U251细胞无明显抑制作用,而高剂量curcumin对U251细胞存在明显的生长抑制作用,生长抑制率达35%。10μMcurcumin作用24h后,U251细胞中ING4蛋白表达水平显著增加。结论高剂量curcumin通过诱导ING4表达上调,抑制脑胶质瘤细胞体外生长。

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简介：Curcumin,adietaryphytochemical,exhibitsmultifunctionalnaturalproductwithregulatoryeffectsoninflammation.However,thepoorbioavailabilitylimitsitsclinicalapplications.Thus,wedesignedandsynthesizedanovelmonocarbonylanalogueofcurcuminB7andtheirinhibitionagainstmonocytechemotacticprotein-1（MCP-1）andinterleukin-8（IL-8）releasewasevaluatedinH2O2-stimulatedhumanvascularendothelialcells（ECs）inadose-responsivemanner,whileexhibitingnocytotoxicityinECs.Takentogether,theseinsightsonthenovelcompoundB7mayserveaspotentialagentsforthetreatmentofatherosclerosis.