Metabolic Patterns and Biotransformation Activities of Resveratrol in Human Glioblastoma Cells Relevance with Therapeutic Efficacies 英文参考文献.docVIP

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Metabolic Patterns and Biotransformation Activities of Resveratrol in Human Glioblastoma Cells Relevance with Therapeutic Efficacies 英文参考文献.doc

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Metabolic Patterns and Biotransformation Activities of Resveratrol in Human Glioblastoma Cells Relevance with Therapeutic Efficacies 英文参考文献

MetabolicPatternsandBiotransformationActivitiesof ResveratrolinHumanGlioblastomaCells:Relevancewith TherapeuticEfficacies Xiao-HongShu1,2,HongLi1,Xiao-XinSun1,QianWang1,ZhengSun1,Mo-LiWu1,Xiao-YanChen1 ,Chong Li1,Qing-YouKong1,JiaLiu1* 1Liaoning Laboratory of Cancer Genetics Epigenetics, Department of Cell Biology, Dalian Medical University, Dalian, China, 2Department of Medicinal Chemistry, CollegeofPharmacy,DalianMedicalUniversity,Dalian,China Abstract Background:Trans-resveratrolratherthanitsbiotransformedmonosulfatemetaboliteexertsanti-medulloblastomaeffects bysuppressingSTAT3activation.Nevertheless,itseffectsonhumanglioblastomacellsarevariableduetocertainunknown reason(s). Methodology/PrincipalFindings:Citingresveratrol-sensitiveUW228-3medulloblastomacelllineandprimarilyculturedrat braincells/PBCsascontrols,theeffectofresveratrolonLN-18humanglioblastomacellsanditsrelevancewithmetabolic pattern(s),brain-associatedsulfotransferase/SULTexpressionandthestatusesofSTAT3signalingandproteininhibitorof activatedSTAT3(PIAS3)wereelucidatedbymultipleexperimentalapproaches.Meanwhile,theexpressionpatternsofthree SULTs(SULT1A1,1C2and4A1)inhumanglioblastomatumorswereprofiledimmunohistochemically.Theresultsrevealed that 100mM resveratrol-treated LN-18 generated the same metabolites as UW228-3 cells, while additional metabolite in molecularweightof403.0992innegativeionmodewasfoundinPBCs.Neithergrowtharrestnorapoptosiswasfoundin resveratrol-treatedLN-18andPBCcells.Uponresveratroltreatment,thelevelsofSULT1A1,1C2and4A1expressioninLN-18 cellsweremoreup-regulatedthanthatexpressedinUW228-3cellsandclosetothelevelsinPBCs.Immunohistochemical stainingshowedthat42.0%,27.1%and19.6%of149glioblastomacasesproducedsimilarSULT1A1,1C2and4A1levelsas thatoftumor-surroundingtissues.UnlikethesituationinUW228-3cells,STAT3signalingremainedactivatedanditsprotein inhibitorPIAS3wasrestrictedinthecytosolofresveratrol-treatedLN-18cells.NonucleartranslocationofSTAT3andPIAS3 wasobservedinresveratrol-treate