title: Distinct sulfonation activities in resveratrol-sensitive and resveratrol-insensitive human glioblastoma cells.
abstract: 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.
authors.affiliation: Liaoning Laboratory of Cancer Genomics and Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Sun
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Shu
authors.forename: Hui
authors.initials: H
authors.lastname: Shi
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Chen
authors.forename: Qing-You
authors.initials: QY
authors.lastname: Kong
authors.forename: Mo-Li
authors.initials: ML
authors.lastname: Wu
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D015239:Arylsulfotransferase / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D013058:Mass Spectrometry; D060787:Neoplasm Grading; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D000077185:Resveratrol; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013267:Stilbenes / Q000494:pharmacology*; D013451:Sulfonic Acids / Q000378:metabolism*; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism*; D046888:Tissue Array Analysis; D014407:Tumor Cells, Cultured
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D012333:RNA, Messenger; D013267:Stilbenes; D013451:Sulfonic Acids; C479953:SULT4A1 protein, human; C513319:SULT1C2 protein, human; D015238:Sulfotransferases; D015239:Arylsulfotransferase; C117544:SULT1A1 protein, human; D000077185:Resveratrol