ArticlePloS one2008
Cell death by SecTRAPs: thioredoxin reductase as a prooxidant killer of cells.
Article in PloS one, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 169 citations in OpenAlex.
- Crosstalk of thioredoxin system and programmed cell death: from pathophysiology to novel therapy.Redox biology · 2026Review
- Transcriptomic Analysis Reveals an NRF2-Mediated Redox and Metabolic Reprogramming in Sorafenib-Resistant Hepatocellular Carcinoma Cells.Biotech (Basel (Switzerland)) · 2026Article
- Targeting Florida red tide: Curcumin inhibits Karenia brevis thioredoxin reductase.Plant physiology and biochemistry : PPB · 2026Article
- Anti-Tumoral Treatment with Thioredoxin Reductase 1 Inhibitor Auranofin Fosters Regulatory T Cell and B16F10 Expansion in Mice.Antioxidants (Basel, Switzerland) · 2025Article
- PK11007 Covalently Inhibits Thioredoxin Reductase 1 to Induce Oxidative Stress and Autophagy Impairment in NSCLC Cells.Antioxidants (Basel, Switzerland) · 2025Article
- Article
- Pharmacological Inhibition of TXNRD1 by a Small Molecule Flavonoid Butein Overcomes Cisplatin Resistance in Lung Cancer Cells.Biological trace element research · 2025Article
- Inhibition of Thioredoxin-Reductase by Auranofin as a Pro-Oxidant Anticancer Strategy for Glioblastoma: In Vitro and In Vivo Studies.International journal of molecular sciences · 2025Review
- Development of a sensor to detect methylmercury toxicity.Scientific reports · 2024Article
- Biosynthesis, Engineering, and Delivery of Selenoproteins.International journal of molecular sciences · 2023Review
- Benzophenanthridine Alkaloid Chelerythrine Elicits Necroptosis of Gastric Cancer Cells via Selective Conjugation at the Redox Hyperreactive C-Terminal SecMolecules (Basel, Switzerland) · 2023Article
- Fluorescent Probes for Mammalian Thioredoxin Reductase: Mechanistic Analysis, Construction Strategies, and Future Perspectives.Biosensors · 2023Review
- Biological and Catalytic Properties of Selenoproteins.International journal of molecular sciences · 2023Review
- Anti-Inflammatory Effect of Dimethyl Fumarate Associates with the Inhibition of Thioredoxin Reductase 1 in RAW 264.7 Cells.Molecules (Basel, Switzerland) · 2022Article
- The Thioredoxin System of Mammalian Cells and Its Modulators.Biomedicines · 2022Review
- Piperlongumine Inhibits Thioredoxin Reductase 1 by Targeting Selenocysteine Residues and Sensitizes Cancer Cells to Erastin.Antioxidants (Basel, Switzerland) · 2022Article
- Delivery of the selenoprotein thioredoxin reductase 1 to mammalian cells.Frontiers in molecular biosciences · 2022Article
- Comprehensive chemical proteomics analyses reveal that the new TRi-1 and TRi-2 compounds are more specific thioredoxin reductase 1 inhibitors than auranofin.Redox biology · 2021Article
- Chlorophyllin Inhibits Mammalian Thioredoxin Reductase 1 and Triggers Cancer Cell Death.Antioxidants (Basel, Switzerland) · 2021Article
- Nrf2 in Cancer, Detoxifying Enzymes and Cell Death Programs.Antioxidants (Basel, Switzerland) · 2021Review
17 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSecTRAPs (selenium compromised thioredoxin reductase-derived apoptotic proteins) can be formed from the selenoprotein thioredoxin reductase (TrxR) by targeting of its selenocysteine (Sec) residue with electrophiles, or by its removal through C-terminal truncation. SecTRAPs are devoid of thioredoxin reductase activity but can induce rapid cell death in cultured cancer cell lines by a gain of function. PRINCIPAL
findingsBoth human and rat SecTRAPs killed human A549 and HeLa cells. The cell death displayed both apoptotic and necrotic features. It did not require novel protein synthesis nor did it show extensive nuclear fragmentation, but it was attenuated by use of caspase inhibitors. The redox active disulfide/dithiol motif in the N-terminal domain of TrxR had to be maintained for manifestation of SecTRAP cytotoxicity. Stopped-flow kinetics showed that NADPH can reduce the FAD moiety in SecTRAPs at similar rates as in native TrxR and purified SecTRAPs could maintain NADPH oxidase activity, which was accelerated by low molecular weight substrates such as juglone. In a cellular context, SecTRAPs triggered extensive formation of reactive oxygen species (ROS) and consequently antioxidants could protect against the cell killing by SecTRAPs.
conclusionsWe conclude that formation of SecTRAPs could contribute to the cytotoxicity seen upon exposure of cells to electrophilic agents targeting TrxR. SecTRAPs are prooxidant killers of cells, triggering mechanisms beyond those of a mere loss of thioredoxin reductase activity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.