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《oligomannurarate sulfate, a novel antimitotic agent, exerts anti-cancer activity by binding to tubulin on novel site》由会员上传分享，免费在线阅读，更多相关内容在工程资料-天天文库。
1、ReseaRChpapeRReseaRChpapeRCancerBiology&Therapy10:1,89-98;July1,2010;©2010LandesBioscienceOligomannuraratesulfate,anovelantimitoticagent,exertsanti-canceractivitybybindingtotubulinonnovelsiteBenchunMiao,1,†YiChen,2,†JingLi,1XianliangXin,1LiGan,1XueyanFu1andMeiyuGeng1,2,*1Department
2、ofpharmacology;MarineDrugandFoodInstitute;OceanUniversityofChina;Qingdao,China;2Divisionofantitumorpharmacology;stateKeyLaboratoryofDrugResearch;shanghaiInstituteofMateriaMedica;Chineseacademyofsciences;shanghai,China†Theseauthorscontributedequallytothiswork.Keywords:JG3,tubulin,an
3、timicrotubuleagent,G/M,antineoplasticagent2Abbreviations:SPR,surfaceplasmonresonance;FITC,fluorescein-5-isothiocyanate;DTNB,5,5'-dithiobis-(2-nitrobenzoicacid);BSA,bovineserumalbumin;DTT,dithiothreitol;IAA,iodoacetamide;FCM,flowcytometry;SDS-PAGE,sodiumdodecylsulfatepolyacrylamideg
4、elelectrophoresis;LC-MS/MS,liquidchromatography-tandemmassspectrometry;bis-ANS,bis-8-anilinonaphthalene-1-sulfonate;RTV,relativetumorvolumeTubulin-bindingagentshavereceivedconsiderableinterestaspotentialanti-cancerdrugs.Thesecompoundsinterferewithtubulindynamicsandmicrotubuleorgani
5、zationandtherebyinducecellgrowtharrestatG/Mphase,andeventually2leadtoapoptoticcelldeath.herein,wereportthatsulfatedoligosaccharideJG3waseffectiveatinhibitingviabilityofcancercells,andsuppressingtumorgrowthinvivo.OurstudiesshowedthatJG3significantlyarrestedcellcycleatG/M2phaseandled
6、cancercellstoapoptoticdeath.Consistentwiththis,tubulinwasidentifiedasabindingproteinofJG3usingaffinitychromatographyandliquidchromatography-tandemmassspectrometry(LC-Ms/Ms).TheinteractionbetweenJG3andtubulinwascharacterizedbysurfaceplasmonresonance(spR)analysis.Furthermore,itwasdem
7、onstratedbothatcellularlevelandincellfreesystemthatJG3potentlypreventedtubulinpolymerization,therebydemolishedmicrotubuleorganizationincancercells.Theunderlyingmechanismliesinitsbindingtotubulinonauniquesitedistinctfromotherconventionalbindingsites.allthesesuggestthatJG3isanovelant
8、imitoticreagent,andthismig
