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: 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
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 79 Issue 10 Pg. 1516-25 (May 15 2010) ISSN: 1873-2968 [Electronic] England
• PMID: 20105429 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: 2010 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Stilbenes
• Sulfotransferases
• Resveratrol

Topics

• 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
• Resveratrol
• Reverse Transcriptase Polymerase Chain Reaction
• Stilbenes (pharmacokinetics, pharmacology)
• Sulfotransferases (metabolism)
• Young Adult