ArticlePloS one2015
Disabling Mitochondrial Peroxide Metabolism via Combinatorial Targeting of Peroxiredoxin 3 as an Effective Therapeutic Approach for Malignant Mesothelioma.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 33 citations in OpenAlex.
- Preclinical characterization and phase 1 clinical testing of targeting mitochondrial peroxiredoxin 3 in cancer.Nature communications · 2026Article
- Metabolic vulnerabilities in pleural mesothelioma.Oncogenesis · 2026Review
- Mechanism-based peroxiredoxin 3 inhibitors exploit a covalent warhead for cancer therapy.Science advances · 2025Article
- Drug-Repurposing Screen Identifies Thiostrepton as a Novel Regulator of the Tumor Suppressor DAB2IP.Biomolecules · 2025Article
- Article
- Proximity-labeling chemoproteomics defines the subcellular cysteinome and inflammation-responsive mitochondrial redoxome.Cell chemical biology · 2023Article
- Inhibition of Mitochondrial Antioxidant Defense and CDK4/6 in Mesothelioma.Molecules (Basel, Switzerland) · 2023Article
- Proximity-labeling chemoproteomics defines the subcellular cysteinome and inflammation-responsive mitochondrial redoxome.bioRxiv : the preprint server for biology · 2023Article
- Unique Cellular and Biochemical Features of Human Mitochondrial Peroxiredoxin 3 Establish the Molecular Basis for Its Specific Reaction with Thiostrepton.Antioxidants (Basel, Switzerland) · 2021Article
- Real-time monitoring of peroxiredoxin oligomerization dynamics in living cells.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Metabolic rewiring and redox alterations in malignant pleural mesothelioma.British journal of cancer · 2020Review
- Peroxiredoxins and Beyond; Redox Systems Regulating Lung Physiology and Disease.Antioxidants & redox signaling · 2019Review
- Small Cell Lung Cancer Therapeutic Responses Through Fractal Measurements: From Radiology to Mitochondrial Biology.Journal of clinical medicine · 2019Article
- Role of Cytosolic 2-Cys Prx1 and Prx2 in Redox Signaling.Antioxidants (Basel, Switzerland) · 2019Review
- Peroxiredoxins in Cancer and Response to Radiation Therapies.Antioxidants (Basel, Switzerland) · 2019Review
- Oxidative stress in chronic lung disease: From mitochondrial dysfunction to dysregulated redox signaling.Molecular aspects of medicine · 2018Review
- Peroxiredoxin Involvement in the Initiation and Progression of Human Cancer.Antioxidants & redox signaling · 2018Review
- Vitamin C in Cancer: A Metabolomics Perspective.Frontiers in physiology · 2018Review
- Activation of the Nrf2-Keap 1 Pathway in Short-Term Iodide Excess in Thyroid in Rats.Oxidative medicine and cellular longevity · 2017Article
- Unique fractal evaluation and therapeutic implications of mitochondrial morphology in malignant mesothelioma.Scientific reports · 2016Article
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
Dysregulation of signaling pathways and energy metabolism in cancer cells enhances production of mitochondrial hydrogen peroxide that supports tumorigenesis through multiple mechanisms. To counteract the adverse effects of mitochondrial peroxide many solid tumor types up-regulate the mitochondrial thioredoxin reductase 2--thioredoxin 2 (TRX2)--peroxiredoxin 3 (PRX3) antioxidant network. Using malignant mesothelioma cells as a model, we show that thiostrepton (TS) irreversibly disables PRX3 via covalent crosslinking of peroxidatic and resolving cysteine residues in homodimers, and that targeting the oxidoreductase TRX2 with the triphenylmethane gentian violet (GV) potentiates adduction by increasing levels of disulfide-bonded PRX3 dimers. Due to the fact that activity of the PRX3 catalytic cycle dictates the rate of adduction by TS, immortalized and primary human mesothelial cells are significantly less sensitive to both compounds. Moreover, stable knockdown of PRX3 reduces mesothelioma cell proliferation and sensitivity to TS. Expression of catalase in shPRX3 mesothelioma cells restores defects in cell proliferation but not sensitivity to TS. In a SCID mouse xenograft model of human mesothelioma, administration of TS and GV together reduced tumor burden more effectively than either agent alone. Because increased production of mitochondrial hydrogen peroxide is a common phenotype of malignant cells, and TS and GV are well tolerated in mammals, we propose that targeting PRX3 is a feasible redox-dependent strategy for managing mesothelioma and other intractable human malignancies.
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