ONC212 Induces Ferroptosis-Associated Cell Death in Glioblastoma Cells

Elif Karabacak; Ceyhan Hacıoğlu

doi:10.18678/dtfd.1914678

ONC212 Induces Ferroptosis-Associated Cell Death in Glioblastoma Cells

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.

Keywords

Ethical Statement

This study does not involve human or animal participants. All procedures followed scientific and ethical principles, and all referenced studies are appropriately cited.

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Details

Primary Language

English

Subjects

Medical Biochemistry and Metabolomics (Other)

Journal Section

Research Article

Authors

Elif Karabacak
0000-0003-2054-4542
Türkiye

Ceyhan Hacıoğlu ^*
0000-0002-0993-6118
Türkiye

Publication Date

August 21, 2026

Submission Date

March 23, 2026

Acceptance Date

July 29, 2026

Published in Issue

Year 2026 Volume: 28 Number: 2

DOI

https://doi.org/10.18678/dtfd.1914678

IZ

https://izlik.org/JA59BN27AK

Cite

RIS / Bibtex

APA

Karabacak, E., & Hacıoğlu, C. (2026). ONC212 Induces Ferroptosis-Associated Cell Death in Glioblastoma Cells. Duzce Medical Journal, 28(2), 181-192. https://doi.org/10.18678/dtfd.1914678

AMA

1.Karabacak E, Hacıoğlu C. ONC212 Induces Ferroptosis-Associated Cell Death in Glioblastoma Cells. Duzce Med J. 2026;28(2):181-192. doi:10.18678/dtfd.1914678

Chicago

Karabacak, Elif, and Ceyhan Hacıoğlu. 2026. “ONC212 Induces Ferroptosis-Associated Cell Death in Glioblastoma Cells”. Duzce Medical Journal 28 (2): 181-92. https://doi.org/10.18678/dtfd.1914678.

EndNote

Karabacak E, Hacıoğlu C (August 1, 2026) ONC212 Induces Ferroptosis-Associated Cell Death in Glioblastoma Cells. Duzce Medical Journal 28 2 181–192.

IEEE

[1]E. Karabacak and C. Hacıoğlu, “ONC212 Induces Ferroptosis-Associated Cell Death in Glioblastoma Cells”, Duzce Med J, vol. 28, no. 2, pp. 181–192, Aug. 2026, doi: 10.18678/dtfd.1914678.

ISNAD

Karabacak, Elif - Hacıoğlu, Ceyhan. “ONC212 Induces Ferroptosis-Associated Cell Death in Glioblastoma Cells”. Duzce Medical Journal 28/2 (August 1, 2026): 181-192. https://doi.org/10.18678/dtfd.1914678.

JAMA

1.Karabacak E, Hacıoğlu C. ONC212 Induces Ferroptosis-Associated Cell Death in Glioblastoma Cells. Duzce Med J. 2026;28:181–192.

MLA

Karabacak, Elif, and Ceyhan Hacıoğlu. “ONC212 Induces Ferroptosis-Associated Cell Death in Glioblastoma Cells”. Duzce Medical Journal, vol. 28, no. 2, Aug. 2026, pp. 181-92, doi:10.18678/dtfd.1914678.

Vancouver

1.Elif Karabacak, Ceyhan Hacıoğlu. ONC212 Induces Ferroptosis-Associated Cell Death in Glioblastoma Cells. Duzce Med J. 2026 Aug. 1;28(2):181-92. doi:10.18678/dtfd.1914678