Document Detail

Distinct sulfonation activities in resveratrol-sensitive and resveratrol-insensitive human glioblastoma cells.
MedLine Citation:
PMID:  22540632     Owner:  NLM     Status:  MEDLINE    
Glioblastoma multiforme (GBM) cells show different responses to resveratrol, for unknown reasons. Our data from human medulloblastoma cells and primary cultures of rat brain cells revealed an inverse correlation of sulfonation activity with resveratrol sensitivities, providing a clue to the underlying mechanisms of the variable sensitivities of GBM cells to resveratrol. In this study, we found that U251 cells were sensitive and LN229 cells were insensitive to resveratrol. Thus, these two cell lines were taken as comparable models for elucidating the influence of sulfonation activities on resveratrol sensitivity. HPLC showed identical resveratrol metabolic patterns in both cell lines. LC/MS and high-resolution mass MS analyses further demonstrated that resveratrol monosulfate generated by sulfotransferases (SULTs) was the major metabolite of human GBM cells. The levels of brain-associated SULT (SULT1A1, SULT1C2, and SULT4A1) expression in U251 cells were lower than those in LN229 cells, suggesting the inverse relationship of SULT-mediated sulfonation activity with high intracellular resveratrol bioavailability and resveratrol sensitivity of human GBM cells. Furthermore, immunohistochemical staining revealed reductions in expression of the three brain-associated SULTs in 72.8%, 47.5% and 66.3% of astrocytomas, respectively. Therefore, the levels of brain-associated SULTs and sulfonation activity mediated by them could be important parameters for evaluating the potential response of human GBM cells to resveratrol, and may have value in the personalized treatment of GBMs with resveratrol.
Zheng Sun; Hong Li; Xiao-Hong Shu; Hui Shi; Xiao-Yan Chen; Qing-You Kong; Mo-Li Wu; Jia Liu
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-05-21
Journal Detail:
Title:  The FEBS journal     Volume:  279     ISSN:  1742-4658     ISO Abbreviation:  FEBS J.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-06-18     Completed Date:  2012-08-21     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  101229646     Medline TA:  FEBS J     Country:  England    
Other Details:
Languages:  eng     Pagination:  2381-92     Citation Subset:  IM    
Copyright Information:
© 2012 The Authors Journal compilation © 2012 FEBS.
Liaoning Laboratory of Cancer Genomics and Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, China.
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MeSH Terms
Antineoplastic Agents, Phytogenic / pharmacology*
Arylsulfotransferase / genetics,  metabolism
Blotting, Western
Brain Neoplasms / drug therapy,  metabolism*
Chromatography, High Pressure Liquid
Drug Resistance, Neoplasm*
Flow Cytometry
Glioblastoma / drug therapy,  metabolism*
Immunoenzyme Techniques
Mass Spectrometry
Neoplasm Grading
RNA, Messenger / genetics
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Stilbenes / pharmacology*
Sulfonic Acids / metabolism*
Sulfotransferases / genetics,  metabolism*
Tissue Array Analysis
Tumor Cells, Cultured
Reg. No./Substance:
0/Antineoplastic Agents, Phytogenic; 0/RNA, Messenger; 0/Stilbenes; 0/Sulfonic Acids; EC 2.8.2/SULT4A1 protein, human; EC 2.8.2.-/SULT1C2 protein, human; EC 2.8.2.-/Sulfotransferases; EC; EC protein, human; Q369O8926L/resveratrol

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