Document Detail


Identification of metabolic pattern and bioactive form of resveratrol in human medulloblastoma cells.
MedLine Citation:
PMID:  20105429     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Xiao-Hong Shu; Hong Li; Zheng Sun; Mo-Li Wu; Jing-Xin Ma; Jian-Min Wang; Qian Wang; Yuan Sun; Yuan-Shan Fu; Xiao-Yan Chen; Qing-You Kong; Jia Liu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-01-25
Journal Detail:
Title:  Biochemical pharmacology     Volume:  79     ISSN:  1873-2968     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-03-09     Completed Date:  2010-04-08     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1516-25     Citation Subset:  IM    
Copyright Information:
2010 Elsevier Inc. All rights reserved.
Affiliation:
Department of Cell Biology, Dalian Medical University, China.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Animals
Antineoplastic Agents / metabolism*,  pharmacokinetics*
Biotransformation
Blotting, Western
Cell Line, Tumor
Cerebellar Neoplasms / drug therapy*
Child
Chromatography, High Pressure Liquid
Humans
Medulloblastoma / drug therapy*
Rats
Reverse Transcriptase Polymerase Chain Reaction
Stilbenes / pharmacokinetics*,  pharmacology
Sulfotransferases / metabolism
Young Adult
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Stilbenes; EC 2.8.2.-/Sulfotransferases; Q369O8926L/resveratrol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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