Hypoxia Dependent Inhibition of Glioblastoma Cell Proliferation, Invasion, and Metabolism by the Choline-Kinase Inhibitor JAS239.

ABSTRACT: Background: Elevated choline kinase alpha (ChoK) levels are observed in most solid tumors, including glioblastomas (GBM), and ChoK inhibitors have demonstrated limited efficacy in GBM models. Given that hypoxia is associated with resistance to GBM therapy, we hypothesized that tumor hypoxia could be responsible for the limited response. Therefore, we evaluated the effects of hypoxia on the function of JAS239, a potent ChoK inhibitor in four GBM cell lines. Methods: Rodent (F98 and 9L) and human (U-87 MG and U-251 MG) GBM cell lines were subjected to 72 h of hypoxic conditioning and treated with JAS239 for 24 h. NMR metabolomic measurements and analyses were performed to evaluate the signaling pathways involved. In addition, cell proliferation, cell cycle progression, and cell

SUBMITTER: Kelly CL 

PROVIDER: S-EPMC11857610 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature