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Updated: Aug 5, 2026
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A Rapid Screening Workflow to Identify Potential Combination Therapy for GBM using Patient-Derived Glioma Stem Cells
Published on: March 28, 2021
Three Thiol-Reactive Reagents drive Synergistic Lethality in Glioblastoma cells
Ofer Y Kashi1, Adi Cohen2, Kathleen Earhart3,4
1Dept. of Biological Chemistry, Institute of Life Sciences, Edmond J Safra Campus Hebrew University of Jerusalem.
Research Square
|July 29, 2026
Summary
A novel triple-thiol cocktail of acrylamide, auranofin, and buthionine sulfoximine effectively kills glioblastoma cells by disrupting redox signaling. This combination shows reduced toxicity in healthy neurons, offering a promising new therapeutic strategy for brain tumors.
Area of Science:
- Oncology
- Neuroscience
- Biochemistry
Background:
- Glioblastoma (GBM) is an aggressive primary brain tumor.
- Disruption of cellular redox balance via cysteine-reactive residues is implicated in GBM progression.
- Targeting redox pathways presents a potential therapeutic avenue for GBM.
Purpose of the Study:
- To investigate the synergistic cytotoxic effects of acrylamide (ACR), auranofin (Auf), and buthionine sulfoximine (DL-BSO) on GBM cells.
- To evaluate the therapeutic potential of a minimal triple-thiol cocktail (ACR/Auf/BSO) for GBM treatment.
- To elucidate the molecular mechanisms underlying the observed synergistic effects and differential toxicity.
Main Methods:
- Treatment of various cancer cell lines and primary rat cortex neuronal cultures with ACR, Auf, and DL-BSO individually and in combination.
- Assessment of cell viability, proliferation, and signaling pathway activation (ERK1/2, p38MAPK, STAT3).
- Measurement of reactive oxygen species (ROS) production in GBM cells and evaluation of a GBM organoid model.
Main Results:
- The ACR/Auf/BSO cocktail demonstrated significant synergistic lethality and suppressed cell growth in multiple cancer cell lines, including GBM.
- This combination induced complete cell death in U87MGMG, U87MGΔEGFR, A431, PC12, and SH-SY5Y cells.
- Minimal toxicity was observed in primary neuronal cultures, which did not activate key survival pathways (ERK1/2, p38MAPK, STAT3).
- The cocktail increased ROS production in patient-derived GBM cells and reduced GBM organoid proliferation.
- Synergy correlated with increased ERK1/2 and p38MAPK phosphorylation and STAT3 inhibition.
Conclusions:
- Combining multiple cysteine-associated redox targets via the ACR/Auf/BSO cocktail is a viable therapeutic strategy for GBM.
- This approach selectively targets GBM cells while sparing healthy neurons.
- The findings suggest a promising new avenue for improving treatment outcomes in GBM and other malignancies.
