Adaptaquin is selectively toxic to glioma stem cells through disruption of iron and cholesterol metabolism.

ABSTRACT: 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 f

SUBMITTER: Vaquie AM 

PROVIDER: S-EPMC7618758 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature