Fig. 4: Oxidative phosphorylation (OXPHOS) and cholesterol biosynthesis are targetable vulnerabilities in oligodendrocyte precursor (OPC)-like gliomaspheres (GS).

A–F Dose-response curves for DIPG-007 GS vs. differentiated glioma cells (DGC) treated with indicated concentrations of mitochondrial OXPHOS inhibitors (i.e. complex I inhibitors) (A) Metformin, (B) Phenformin, and (C) IACS-010759 (IACS), or statins (D) Atorvastatin, (E) Fluvastatin, and (F) Pitavastatin for 3 days or 7 days (Metformin). Cell viability was assayed using Cell Titer-Glo 2.0 (DGC) or 3D (GS) and results expressed as percent of vehicle control (0.1% DMSO). Error bars for panels A–F represent mean ± SD from three biological replicates (****p < 0.0001 by area under proliferation curve test followed by two-tailed Student’s t-test). G, H) Western blot analysis of PARP cleavage (apoptosis indicator) with an α-TUBULIN loading control in (G) Phenformin (Phen)-treated and (H) Pitavastatin (Pita)-treated DIPG007 DGC and GS. The figure shows representative blots from two independent experiments. Cells were treated for 48 h at the indicated concentrations. For panels A–F, red indicates GS; blue, DGC.