title: Identification of metabolic pattern and bioactive form of resveratrol in human medulloblastoma cells.
abstract: Cancer preventive reagent trans-resveratrol is intracellularly biotransformed to different metabolites. However, it is still unclear whether trans-resveratrol exerts its biological effects directly or through its metabolite(s). This issue was addressed here by identifying the metabolic pattern and the bioactive form of resveratrol in a resveratrol-sensitive human medulloblastoma cell line, UW228-3. The cell lysates and condition media of UW228-3 cells with or without 100 microM resveratrol treatment were analyzed by HPLC and LC/MS which revealed (1) that resveratrol was chemically unstable and the spontaneous generation of cis-resveratrol reduced resveratrol's anti-medulloblastoma efficacy and (2) that resveratrol monosulfate was the major metabolite of the cells. To identify the bioactive form of resveratrol, a mixture-containing approximately half fraction of resveratrol monosulfate was prepared by incubating trans-resveratrol with freshly prepared rat brain lysates. Medulloblastoma cells treated by 100 microM of this mixture showed attenuated cell crisis. The overall levels of the three brain-associated sulfotransferases (SULT1A1, 1C2 and 4A1) were low in medulloblastoma cells in vivo and in vitro in comparison with that in human noncancerous and rat normal cerebella; resveratrol could more or less up-regulate the production of these enzymes in UW228-3 cells but their overall level was still lower than that in normal cerebellum tissue. Our study thus demonstrated for the first time that trans-resveratrol is the bioactive form in medulloblastoma cells in which the expression of brain-associated SULTs was down-regulated, resulting in the increased intracellular bioavailability and anti-medulloblastoma efficacy of trans-resveratrol.
authors.affiliation: Department of Cell Biology, Dalian Medical University, China.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Shu
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Zheng
authors.initials: Z
authors.lastname: Sun
authors.forename: Mo-Li
authors.initials: ML
authors.lastname: Wu
authors.forename: Jing-Xin
authors.initials: JX
authors.lastname: Ma
authors.forename: Jian-Min
authors.initials: JM
authors.lastname: Wang
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Sun
authors.forename: Yuan-Shan
authors.initials: YS
authors.lastname: Fu
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Chen
authors.forename: Qing-You
authors.initials: QY
authors.lastname: Kong
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
mesh_terms: D000293:Adolescent; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism* / Q000493:pharmacokinetics*; D001711:Biotransformation; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002528:Cerebellar Neoplasms / Q000188:drug therapy*; D002648:Child; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D008527:Medulloblastoma / Q000188:drug therapy*; D051381:Rats; D000077185:Resveratrol; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013267:Stilbenes / Q000493:pharmacokinetics* / Q000494:pharmacology; D015238:Sulfotransferases / Q000378:metabolism; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D013267:Stilbenes; D015238:Sulfotransferases; D000077185:Resveratrol