Disulfiram, a Ferroptosis Inducer, Triggers Lysosomal Membrane Permeabilization by Up-Regulating ROS in Glioblastoma
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Updated: Dec 3, 2025
Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
Chen Qiu1,2,3, Xin Zhang3,4, Bin Huang3,4
1Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan, People's Republic of China.
Introduction:
Disulfiram (DSF), a drug used in the treatment of alcoholism since 1948, has been shown to have antitumor properties in various tumor types possibly due to the induction of a type cell death, ferroptosis, and the sensitization of cells to chemo- and radiotherapy. In this study, we explored the antitumor properties of DSF in glioblastoma (GBM) and investigated the underlying molecular mechanisms.
Methods:
GBM cell lines U251 and LN229 were treated with DSF to assess cytotoxicity and activity of the molecule in vitro. Response of cells to treatment was examined using cell viability, flow cytometry, LDH release assay, immunofluorescence and Western blot analysis.
Results:
DSF inhibited cell growth of GBM U251 and LN229 cell lines in vitro in a concentration-dependent manner. Flow cytometry demonstrated that DSF caused G0-G1 growth arrest. DSF treatment led to increased ROS and lipid peroxidation levels relative to controls indicating the involvement of ferroptosis. Furthermore, DSF triggered lysosomal membrane permeabilization (LMP), a critical mechanism promoting cell death, in a ROS-dependent manner. Finally, DSF enhanced radiosensitivity of U251 and LN229 cells.
Discussion:
Our findings indicated that DSF induced ferroptosis and LMP and enhanced the radiosensitivity of GBM cells. Therefore, DSF might have efficient antitumor activity in the treatment of human GBM.
Insights
Disulfiram (DSF) shows antitumor potential against glioblastoma (GBM) by inducing ferroptosis and lysosomal membrane permeabilization. This drug also enhances GBM cell radiosensitivity, suggesting a promising therapeutic option.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Disulfiram (DSF), an alcoholism treatment, exhibits antitumor properties.
- DSF may induce ferroptosis and sensitize cancer cells to therapy.
- Glioblastoma (GBM) is an aggressive brain tumor with limited treatment options.
Purpose of the Study:
- To investigate the antitumor effects of DSF in glioblastoma (GBM).
- To elucidate the molecular mechanisms underlying DSF's action in GBM cells.
Main Methods:
- GBM cell lines (U251, LN229) were treated with DSF.
- Assessed cytotoxicity, cell viability, and growth arrest (flow cytometry).
- Analyzed reactive oxygen species (ROS), lipid peroxidation, and lysosomal membrane permeabilization (LMP).
Main Results:
- DSF inhibited GBM cell growth in a dose-dependent manner.
- DSF induced G0-G1 cell cycle arrest, increased ROS, and lipid peroxidation, indicating ferroptosis.
- DSF triggered ROS-dependent LMP and enhanced GBM cell radiosensitivity.
Conclusions:
- DSF induces ferroptosis and LMP in GBM cells.
- DSF enhances the radiosensitivity of GBM cells.
- DSF demonstrates potential as an effective therapeutic agent for human GBM.
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