biostudies-literatureUnknownVaquie AMDr. Miriam and Sheldon G. Adelson Medical Research FoundationSwiss National Science foundation (SNSF)European Research CouncilNIHR Cambridge Biomedical Research CentreNational Institute for Health Research (NIHR)Dr Miriam and Sheldon G. Adelson Medical Research FoundationGlioma stem cells (GSCs) from this aggressive brain cancer have been subject to nononcogene addiction therapeutic strategies, in particular targeting iron and cholesterol metabolic pathways. In this study, we show the small molecule Adaptaquin (AQ) has anti-GSC effects while sparing neurons, mature oligodendrocytes and astrocytes. Transcriptomic analysis of AQ-treated GSCs showed dramatic upregulation of iron transport genes and downregulation of genes involved in cholesterol biosynthesis. Indeed, we found cytotoxic effects of AQ on GSCs were potentiated when combined with the iron chelator deferoxamine (DFO). Notably, these effects were independent of PHD2 and HIF1α regulation, indicating a distinct pathway of action. Furthermore, we observed that the heme analogue, hemin, protects GSCs fMolecular oncologyhttps://www.ebi.ac.uk/biostudies/studies/S-EPMC7618758biostudies-literatureAdaptaquin is selectively toxic to glioma stem cells through disruption of iron and cholesterol metabolism.PMC7618758P2FRP3_188056NIHR203312789054Morcom LPathania MGold Diaz DGirdler GCNathan JAMcNicholas MBalmus GBrindle KMVaquie AMStockley JHShah DRBrechbuhl EESBulstrode HRatan RRSeear RVRowitch DHXu ZfalseAdaptaquin is selectively toxic to glioma stem cells through disruption of iron and cholesterol metabolism.Glioma stem cells (GSCs) from this aggressive brain cancer have been subject to nononcogene addiction therapeutic strategies, in particular targeting iron and cholesterol metabolic pathways. In this study, we show the small molecule Adaptaquin (AQ) has anti-GSC effects while sparing neurons, mature oligodendrocytes and astrocytes. Transcriptomic analysis of AQ-treated GSCs showed dramatic upregulation of iron transport genes and downregulation of genes involved in cholesterol biosynthesis. Indeed, we found cytotoxic effects of AQ on GSCs were potentiated when combined with the iron chelator deferoxamine (DFO). Notably, these effects were independent of PHD2 and HIF1α regulation, indicating a distinct pathway of action. Furthermore, we observed that the heme analogue, hemin, protects GSCs f2025-01-01T00:00:00Z2025 Sep2026-07-09T11:04:33.134Z2026-07-09T10:39:08.886ZS-EPMC76187584097587610.1002/1878-0261.70128