The contribution of ketone bodies to glycolytic inhibition for the treatment of adult and pediatric glioblastoma

This study examined ketone body metabolism in glioblastoma (GBM) using patient database expression data and GBM and glioblastoma stem-like cell (GSC) lines. The enzymes needed for ketone catabolism (BDH1, OXCT1 and ACAT1) were significantly downregulated in adult and pediatric GBM. Acetoacetate (AA) and the glycolytic inhibitor 2-deoxy-D-glucose reduced cell viability dose-dependently, but beta-hydroxybutyrate did not. AA induced apoptosis and reduced neurosphere formation at concentrations as low as 1 mM, and low-dose 2-DG (50 µM) combined with AA caused more cell death than either alone, reducing viability by approximately 50 percent at 1 mM AA.