ArticleCell death and differentiation2025
Inhibition of thioredoxin reductase 1 sensitizes glucose-starved glioblastoma cells to disulfidptosis.
Article in Cell death and differentiation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed.
- Disulfidptosis: molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Evading disulfidptosis via NRF2 translation.Nature cell biology · 2026Article
- The mitochondria enzyme OGDH defends against disulfidptosis by licensing METTL3-regulated NRF2 translation.Nature cell biology · 2026Article
- Disulfidptosis: Mechanisms, evidence boundaries, and translational opportunities.Redox biology · 2026Review
- Experimental Detection Methods and Clinical Translational Challenges of Disulfidptosis in Cancer.Cells · 2026Review
- Metabolic cell death: ferroptosis, cuproptosis, and disulfidptosis as a unified framework for targeting metabolic vulnerabilities in disease.Apoptosis : an international journal on programmed cell death · 2026Review
- Disulfidptosis and its molecular mechanisms in cancer: mechanisms, regulation, and therapeutic potential.Medical oncology (Northwood, London, England) · 2026Review
- Crosstalk of thioredoxin system and programmed cell death: from pathophysiology to novel therapy.Redox biology · 2026Review
- Review
- Dual metabolic intervention nanoplatform co-delivering BAY-876 and L-cystine for Wilms tumor therapy via disulfidptosis-associated cytoskeletal collapse.Journal of nanobiotechnology · 2026Article
- The emerging role of disulfidptosis in metabolic synergistic death and cancer immunotherapy.Oncogenesis · 2026Review
- Article
- Disulfidptosis: The metabolic Achilles' heel of SLC7A11-high tumors and why oncology has missed it.Annals of medicine and surgery (2012) · 2026Article
- Disulfidptosis in hepatocellular carcinoma: molecular mechanisms, therapeutic potential, and exploratory insights into chronic liver diseases.Apoptosis : an international journal on programmed cell death · 2026Review
- Disulfidptosis vs. Ferroptosis: A Comprehensive Review of SLC7A11-Mediated Metal Dyshomeostasis and Cell Death.Biomolecules · 2026Review
- [Exploring the protective effects and mechanisms of HYX1-derived exosomes on acute liver failure based on disulfidptosis signaling].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Article
- RRx-001 inhibits G6PD to deplete NADPH and trigger disulfidptosis coupled with DAMP-mediated immunogenic cell death in hepatocellular carcinoma.Cell death discovery · 2026Article
- Exercise and CD8Journal of molecular medicine (Berlin, Germany) · 2026Review
- The Mechanism and Regulation of Disulfidptosis and Its Role in Disease.Biomedicines · 2026Review
- Metabolic cell death networks in Alzheimer's disease: mechanistic links and therapeutic perspectives of ferroptosis, cuproptosis, and disulfidptosis.Frontiers in cell and developmental biology · 2026Review
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Disulfidptosis is a recently identified form of cell death characterized by the aberrant accumulation of cellular disulfides. This process primarily occurs in glucose-starved cells expressing higher levels of SLC7A11 and has been proposed as a therapeutic strategy for cancers with hyperactive SCL7A11. However, the potential for inducing disulfidptosis through other mechanisms in cancers remains unclear. Here, we found that inhibiting thioredoxin reductase 1 (TrxR1), a key enzyme in the thioredoxin system, induces disulfidptosis in glioblastoma (GBM) cells. TrxR1 expression is elevated in GBM with activated transcriptional coactivator with PDZ-binding motif (TAZ) and correlates with poor prognosis. TrxR1 inhibitors induced GBM cell death that can be rescued by disulfide reducers but not by ROS scavengers or inhibitors of apoptosis, ferroptosis, or necroptosis. Glucose-starved cells, but not those deprived of oxygen or glutamine, increased TrxR1 expression in an NRF2-dependent manner and were more sensitive to TrxR1 inhibition-induced cell death. The dying cells initially exhibited highly dynamic lamellipodia, followed by actin cytoskeleton collapse. This process involved the accumulation of cytosolic peroxisomes and micropinocytic caveolae, as well as small gaps in the plasma membrane. Depletion of the WAVE complex component NCKAP1 partially rescued the cells, whereas Rac inhibition enhanced cell death. In an orthotopic xenograft GBM mouse model, TrxR1 depletion inhibited tumor growth and improved survival. Furthermore, cells undergoing TrxR1 inhibition exhibited features of immunogenic cell death. Therefore, this study suggests the potential of targeting TrxR1 as a therapeutic strategy in GBM.
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