Journal
BIOCHEMICAL PHARMACOLOGY
Volume 79, Issue 10, Pages 1516-1525Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2010.01.022
Keywords
Resveratrol; Medulloblastoma; Drug metabolism; Sulfotransferase; Chemosensitivity
Categories
Funding
- National Natural Science Foundation of China [30527002, 30670946, 30971038]
- Liaoning Department of Education [20060193]
- creative research team [2007-7-26, 2008T028]
Ask authors/readers for more resources
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 mu M 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 mu M 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. (C) 2010 Elsevier Inc All rights reserved
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available