Elif KARABACAK, Ceyhan HACIOĞLU
Düzce Tıp Fakültesi Dergisi - 2026;28(2):181-192
Aim : Glioblastoma (GBM) is an aggressive primary brain tumor with limited treatment options. Ferroptosis, an iron -dependent cell death characterized by lipid peroxidation and oxidative stress, is a promising therapeutic target. This study investigated the antic ancer effects of the imipridone derivative ONC212 in GBM cells and examined whether its cytotoxicity involves ferroptosis -related mechanisms. Material and Methods : U87 and U251 cells were treated with increasing ONC212 concentrations. Viability was assessed by CCK -8, proliferation by BrdU incorporation (24-72 h). Ferroptosis -associated changes were evaluated by measuring ferrous iron (Fe²?), malondialdehyde (MDA), gl utathione (GSH), and reactive oxygen species (ROS). Expression of ferroptosis -related genes GPX4 and ACSL4 was analyzed by qRT -PCR. Ferrostatin -1 (Fer -1) was used to confirm ferroptosis involvement. Results : ONC212 reduced viability in a time - and dose -dependent manner [IC?? (95% CI): 18.7 µM (17.3 -20.1), 9.6 µM (8.8 -10.4), and 6.2 µM (5.7 -6.7) at 24, 48, and 72 h, respectively]. BrdU incorporation decreased by 46.9% and 79.4% at 24 h and 72 h, respectively, f ollowing treatment with the 24 -hour IC?? concentration (18.7 µM). Ferroptosis -associated oxidative stress was evident through increased Fe²?, MDA, ROS, and GSH depletion. ONC212 upregulated ACSL4 (2.14-fold) and reduced GPX4 expression by 62%. Fer -1 pretre atment partially reversed these alterations, supporting the involvement of ferroptosis -associated mechanisms. Similar results were obtained in U251 cells. Conclusion : ONC212 exerts potent cytotoxic and anti -proliferative effects in GBM cells and provides preliminary evidence suggesting that it induces ferroptosis -associated cell death through modulation of oxidative stress and ferroptosis-associated gene expression. Targeting ferroptosis with ONC212 may represent a promising therapeutic strategy for GBM.
