Distinct sulfonation activities in resveratrol-sensitive and resveratrol-insensitive human glioblastoma cells
Distinct sulfonation activities in resveratrol-sensitive and resveratrol-insensitive human glioblastoma cells
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白藜芦醇敏感和白藜芦醇不敏感的人胶质母细胞瘤细胞具有不同的磺化活性
DOI：
10.1111/j.1742-4658.2012.08617.x
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发表时间：
2012-07-01
期刊：
影响因子：
5.4
通讯作者：
Liu, Jia
中科院分区：
文献类型：
--
作者：
Sun, Zheng;Li, Hong;Liu, Jia
多形性胶质母细胞瘤（GBM）细胞对白藜芦醇表现出不同的反应，原因不明。我们从人髓母细胞瘤细胞和大鼠脑细胞的原代培养中获得的数据显示，磺化活性与白藜芦醇敏感性呈负相关，为GBM细胞对白藜芦醇可变敏感性的潜在机制提供了线索。本研究发现U251细胞对白藜芦醇敏感，而LN229细胞对白藜芦醇不敏感。因此，这两种细胞系被作为可比较的模型来阐明磺化活性对白藜芦醇敏感性的影响。HPLC显示两种细胞系的白藜芦醇代谢模式相同。LC/MS和高分辨率质谱分析进一步证实，硫酸盐转移酶（SULTs）产生的单硫酸白藜芦醇是人GBM细胞的主要代谢物。脑相关SULT （SULT1A1、SULT1C2和SULT4A1）在U251细胞中的表达水平低于LN229细胞，表明SULT介导的磺化活性与人GBM细胞高白藜芦醇生物利用度和白藜芦醇敏感性呈反比关系。此外，免疫组织化学染色显示，三种脑相关SULTs的表达分别在72.8%、47.5%和66.3%的星形细胞瘤中降低。因此，脑相关SULTs水平及其介导的磺化活性可能是评估人GBM细胞对白藜芦醇潜在反应的重要参数，并可能在白藜芦醇个体化治疗GBM中具有价值。数据库?SULT1A1、SULT1C2和SULT4A1的核苷酸序列数据可在GenBank数据库中获得，登录号为，和。
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. Database ?Nucleotide sequence data for SULT1A1, SULT1C2 and SULT4A1 are available in the GenBank database under the accession numbers , , and .