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首页> 外文期刊>Journal of Cellular Physiology >Acetate Supplementation as a Means of Inducing Glioblastoma Stem-Like Cell Growth Arrest
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Acetate Supplementation as a Means of Inducing Glioblastoma Stem-Like Cell Growth Arrest

机译：醋酸诱导的作为补充手段恶性胶质瘤干细胞样细胞生长被捕

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Glioblastoma (GBM), the most common primary adult malignant brain tumor, is associated with a poor prognosis due, in part, to tumor recurrence mediated by chemotherapy and radiation resistant glioma stem-like cells (GSCs). The metabolic and epigenetic state of GSCs differs from their non-GSC counterparts, with GSCs exhibiting greater glycolytic metabolism and global hypoacetylation. However, little attention has been focused on the potential use of acetate supplementation as a therapeutic approach. N-acetyl-l-aspartate (NAA), the primary storage form of brain acetate, and aspartoacylase (ASPA), the enzyme responsible for NAA catalysis, are significantly reduced in GBM tumors. We recently demonstrated that NAA supplementation is not an appropriate therapeutic approach since it increases GSC proliferation and pursued an alternative acetate source. The FDA approved food additive Triacetin (glyceryl triacetate, GTA) has been safely used for acetate supplementation therapy in Canavan disease, a leukodystrophy due to ASPA mutation. This study characterized the effects of GTA on the proliferation and differentiation of six primary GBM-derived GSCs relative to established U87 and U251 GBM cell lines, normal human cerebral cortical astrocytes, and murine neural stem cells. GTA reduced proliferation of GSCs greater than established GBM lines. Moreover, GTA reduced growth of the more aggressive mesenchymal GSCs greater than proneural GSCs. Although sodium acetate induced a dose-dependent reduction of GSC growth, it also reduced cell viability. GTA-mediated growth inhibition was not associated with differentiation, but increased protein acetylation. These data suggest that GTA-mediated acetate supplementation is a novel therapeutic strategy to inhibit GSC growth. J. Cell. Physiol. 230: 1929-1943, 2015. (c) 2015 Wiley Periodicals, Inc.
机译：胶质母细胞瘤(GBM),最常见的成人恶性脑瘤,与贫穷有关部分预后因肿瘤复发由耐化疗和放疗神经胶质瘤干细胞样细胞(gsc)。表观遗传状态gsc与他们不同non-GSC同行,gsc展出更大的糖酵解代谢和全球hypoacetylation。集中在乙酸的潜在用途补充治疗方法。N-acetyl-l-aspartate (NAA),主存储醋酸的大脑,aspartoacylase (ASPA),负责乙酰天冬氨酸酶催化的在GBM肿瘤显著降低。乙酰天冬氨酸补充证明不是一个适当的治疗方法,因为它增加GSC扩散和追求醋酸替代来源。添加剂三醋精(三乙酸甘油酯,侠盗猎车手)被安全地用于醋酸的补充在Canavan疾病治疗,脑白质营养不良ASPA突变。侠盗猎车手对扩散的影响分化的六个主要GBM-derived gsc相对于建立U87和U251细胞“绿带运动”线,正常的人类大脑皮质星形胶质细胞,和小鼠神经干细胞。gsc大于扩散“绿带运动”。更激进的间充质gsc大于颈板gsc。剂量依赖性降低GSC增长,它也减少细胞的可行性。抑制无关分化,但增加蛋白质乙酰化作用。补充乙酸酯是一种新型的治疗策略来抑制GSC生长。230: 1929 - 1943, 2015。公司。

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