Fig. 2

PCI-24781 potentially decreases the DNA repair machinery and activates apoptotic signaling (A-C) Pathways: The web-based iLINCS server was used to assess the associated signatures for each of the top 3 scoring drugs. Pathways affected by PCI-24781 (A), belinostat (B), and vorinostat (C). Interestingly, PCI-24781 has a unique signature when compared to pan-HDAC inhibitors and specifically impacts apoptotic signaling. D DNA repair machinery expression in GBM Using GEPIA on 163 GBM tumors (red) and 207 controls (black) show that DNA repair machinery genes BRCA1, RAD51, CHK1, and Ku70 are significantly upregulated in GBM when compared to control (p < 0.01). E PCI-24781 effectively decreases the DNA repair machinery in U-118MG GBM cells. U-118MG cells were treated with 1.5 μM of HDAC inhibitor for 48 h, and lysates were analyzed for DNA repair machinery proteins by immunoblotting. The extent of acetylation of α tubulin supports the efficacy of PCI-24781. DMSO served as vehicle control. F U-118MG cells were treated with 1.5 μM of HDAC inhibitor for 48 h, and lysates were analyzed for apoptotic markers cleaved PARP (CST- 9541; recognize cleaved PARP, not total) and cleaved caspase 3