Acetate supplementation as a means of inducing glioblastoma stem-like cell growth arrest.
Acetate supplementation as a means of inducing glioblastoma stem-like cell growth arrest.
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补充乙酸作为诱导胶质母细胞瘤干细胞生长停滞的一种手段。
DOI：
10.1002/jcp.24927
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发表时间：
2015-08
影响因子：
5.6
通讯作者：
Jaworski, Diane M.
中科院分区：
文献类型：
--
作者：
Long, Patrick M.;Tighe, Scott W.;Driscoll, Heather E.;Fortner, Karen A.;Viapiano, Mariano S.;Jaworski, Diane M.
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.
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影响因子：
56.9
作者：
Choudhary, Chunaram;Kumar, Chanchal;Mann, Matthias
通讯作者：
Mann, Matthias
影响因子：
9.3
作者：
Brissette CA;Houdek HM;Floden AM;Rosenberger TA
通讯作者：
Rosenberger TA
影响因子：
4.2
作者：
Bhatt DP;Houdek HM;Watt JA;Rosenberger TA
通讯作者：
Rosenberger TA
影响因子：
6.4
作者：
Anderson KA;Hirschey MD
通讯作者：
Hirschey MD
影响因子：
4.2
作者：
Gryder BE;Sodji QH;Oyelere AK
通讯作者：
Oyelere AK