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

[canavan disease]

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 Hs 683 oligodendroglioma , U 87 and U 251 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 .

Diseases
Validation

Diseases presenting "cancer" symptom

achondroplasia

acute rheumatic fever

adrenal incidentaloma

alpha-thalassemia

benign recurrent intrahepatic cholestasis

cadasil

canavan disease

carcinoma of the gallbladder

cholangiocarcinoma

coats disease

congenital adrenal hyperplasia

congenital diaphragmatic hernia

cowden syndrome

cushing syndrome

cutaneous mastocytosis

dedifferentiated liposarcoma

dystrophic epidermolysis bullosa

epidermolysis bullosa simplex

erdheim-chester disease

erythropoietic protoporphyria

esophageal adenocarcinoma

esophageal carcinoma

esophageal squamous cell carcinoma

familial hypocalciuric hypercalcemia

familial mediterranean fever

gm1 gangliosidosis

heparin-induced thrombocytopenia

hereditary cerebral hemorrhage with amyloidosis

hirschsprung disease

hodgkin lymphoma, classical

inclusion body myositis

junctional epidermolysis bullosa

kabuki syndrome

kallmann syndrome

kindler syndrome

lamellar ichthyosis

liposarcoma

locked-in syndrome

lymphangioleiomyomatosis

monosomy 21

neuralgic amyotrophy

oculocutaneous albinism

oligodontia

oral submucous fibrosis

papillon-lefèvre syndrome

pendred syndrome

pleomorphic liposarcoma

primary effusion lymphoma

proteus syndrome

pyomyositis

pyruvate dehydrogenase deficiency

severe combined immunodeficiency

sneddon syndrome

systemic capillary leak syndrome

triple a syndrome

von hippel-lindau disease

waldenström macroglobulinemia

well-differentiated liposarcoma

werner syndrome

wiskott-aldrich syndrome

wolf-hirschhorn syndrome

x-linked adrenoleukodystrophy

This symptom has already been validated