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Triacetin-based acetate supplementation as a chemotherapeutic adjuvant therapy in glioma.

Al's Comment:

 This article shows that - in the lab - a common food additive that has been deemed "safe" by the FDA may have anti tumor properties and in the test tube may help Temodar work better. Of course, this isn't in humans so we do not know yet if it would help people, but I love the idea of using a readily available, cheap, nontoxic to increase the chances that Temodar would help..

 


Posted on: 09/14/2013

Int J Cancer. 2013 Aug 30. doi: 10.1002/ijc.28465. [Epub ahead of print]
Triacetin-based acetate supplementation as a chemotherapeutic adjuvant therapy in glioma.
Tsen AR, Long PM, Driscoll HE, Davies MT, Teasdale BA, Penar PL, Pendlebury WW, Spees JL, Lawler SE, Viapiano MS, Jaworski DM.
University of Vermont (UVM) College of Medicine (COM), Department of Surgery Division of Neurosurgery, Burlington, VT, 05405.
 
Abstract
Cancer is associated with epigenetic (i.e., histone hypoacetylation) and metabolic (i.e., aerobic glycolysis) alterations. Levels of N-acetyl-L-aspartate (NAA), the primary storage form of acetate in the brain, and aspartoacylase (ASPA), the enzyme responsible for NAA catalysis to generate acetate, are reduced in glioma; yet, few studies have investigated acetate as a potential therapeutic agent. This preclinical study sought to test the efficacy of the food additive Triacetin (glyceryl triacetate, GTA) as a novel therapy to increase acetate bioavailability in glioma cells. The growth-inhibitory effects of GTA, compared to the histone deacetylase inhibitor Vorinostat (SAHA), were assessed in established human glioma cell lines (HOG and Hs683 oligodendroglioma, U87 and U251 glioblastoma) and primary tumor-derived glioma stem-like cells (GSCs), relative to an oligodendrocyte progenitor line (Oli-Neu), normal astrocytes, and neural stem cells (NSCs) in vitro. GTA was also tested as a chemotherapeutic adjuvant with temozolomide (TMZ) in orthotopically grafted GSCs. GTA induced cytostatic growth arrest in vitro comparable to Vorinostat, but, unlike Vorinostat, GTA did not alter astrocyte growth and promoted NSC expansion. GTA alone increased survival of mice engrafted with glioblastoma GSCs and potentiated TMZ to extend survival longer than TMZ alone. GTA was most effective on GSCs with a mesenchymal cell phenotype. Given that GTA has been chronically administered safely to infants with Canavan disease, a leukodystrophy due to ASPA mutation, GTA-mediated acetate supplementation may provide a novel, safe chemotherapeutic adjuvant to reduce the growth of glioma tumors, most notably the more rapidly proliferating, glycolytic, and hypoacetylated mesenchymal glioma tumors. © 2013 Wiley Periodicals, Inc.
 

 


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