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Journals / Düzce Tıp Fakültesi Dergisi / 2026 / Volume: 28 Issue: 2

ONC212 Induces Ferroptosis-Associated Cell Death in Glioblastoma Cells

Elif Karabacak(DUZCE UNIVERSITY)0000-0003-2054-4542
Ceyhan Hacıoğlu(DUZCE UNIVERSITY)0000-0002-0993-6118
Pages
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Publication Date
2026-08-21
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

Targeting ferroptosis with ONC212 may represent a promising therapeutic strategy for GBM.

📌 3 Key Takeaways

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Objective & Hypothesis:Aim: Glioblastoma (GBM) is an aggressive primary brain tumor with limited treatment options.
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Key Findings & Data:This study investigated the anticancer effects of the imipridone derivative ONC212 in GBM cells and examined whether its cytotoxicity involves ferroptosis-related mechanisms.
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Conclusion & Impact:Targeting ferroptosis with ONC212 may represent a promising therapeutic strategy for GBM.
🔬Design:Research Article
📍Scope:Comprehensive Sample
⚙️Variables:Glioblastoma · imipridone · ONC212

Abstract

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 anticancer 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), glutathione (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 [IC₅₀ (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, following treatment with the 24-hour IC₅₀ 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 pretreatment 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.

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Cite This Article

Karabacak, E., Hacıoğlu, C. (2026). ONC212 Induces Ferroptosis-Associated Cell Death in Glioblastoma Cells. Düzce Tıp Fakültesi Dergisi, Volume: 28 Issue: 2. https://doi.org/10.18678/dtfd.1914678

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