ArticleFree radical biology & medicine2009
Increase in thiol oxidative stress via glutathione reductase inhibition as a novel approach to enhance cancer sensitivity to X-ray irradiation.
Article in Free radical biology & medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 56 citations in OpenAlex.
- Glutathione reductase deficiency potentiates the immunogenicity of ferroptosis and cuproptosis via amplified reactive oxygen species accumulation and cGAS-STING pathway activation.Journal of hematology & oncology · 2026Article
- Redox Modulation in Therapy of Cancer: Some Pros and Cons.Antioxidants (Basel, Switzerland) · 2025Review
- Novel Pyrroloquinoline Quinone-Modified Cerium Oxide Nanoparticles and Their Selective Cytotoxicity Under X-Ray Irradiation.Antioxidants (Basel, Switzerland) · 2024Article
- Antioxidant Enzymes and Their Potential Use in Breast Cancer Treatment.International journal of molecular sciences · 2024Review
- Glutathione Reductase Expression and Its Prognostic Significance in Colon Cancer.International journal of molecular sciences · 2024Article
- Chemical profiling of volatile compounds of the essential oil of grey-leaved rockrose (Frontiers in chemistry · 2024Article
- Application of nano-radiosensitizers in combination cancer therapy.Bioengineering & translational medicine · 2023Review
- The Effects of Antioxidant Nutraceuticals on Cellular Sulfur Metabolism and Signaling.Antioxidants & redox signaling · 2023Review
- The Role of the Thioredoxin Detoxification System in Cancer Progression and Resistance.Frontiers in molecular biosciences · 2022Review
- Role of NRF2 in Lung Cancer.Cells · 2021Review
- Cysteine and Folate Metabolism Are Targetable Vulnerabilities of Metastatic Colorectal Cancer.Cancers · 2021Article
- Review
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- Impact of Oxidative Stress and Protein S-Glutathionylation in Aortic Valve Sclerosis Patients with Overt Atherosclerosis.Journal of clinical medicine · 2019Article
- Rational design of reversible fluorescent probes for live-cell imaging and quantification of fast glutathione dynamics.Nature chemistry · 2017Article
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- Article
- MitoNEET Protects HL-1 Cardiomyocytes from Oxidative Stress Mediated Apoptosis in an In Vitro Model of Hypoxia and Reoxygenation.PloS one · 2016Article
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- Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Depletion of the reduced form of glutathione (GSH) has been extensively studied for its effect on sensitizing cancer to radiation. However, little is known about the effects of thiol oxidative stress created through an increase in glutathione disulfide (GSSG) on cancer sensitivity to radiation. In this study, an increase in GSSG was effectively created using 2-acetylamino-3-[4-(2-acetylamino-2-carboxyethylsulfanylthiocarbonylamino)phenylthiocarbamoylsulfanyl]propionic acid (2-AAPA), an irreversible glutathione reductase (GR) inhibitor. Our results demonstrate that the GSSG increase significantly enhanced cancer sensitivity to X-ray irradiation in four human cancer cell lines (A431, MCF7, NCI-H226, and OVCAR-3). When cells were pretreated with 2-AAPA followed by X-ray irradiation, the IC(50) values for X-ray irradiation of A431, MCF7, NCI-H226, and OVCAR-3 cells were reduced, from 24.2 +/- 2.8, 42.5 +/- 3.0, 43.0 +/- 3.6, and 27.8+/-3.5 Gy to 6.75 +/- 0.9, 8.1 +/- 1.1, 6.75 +/- 1.0, and 12.1 +/- 1.7 Gy, respectively. The synergistic effects observed from the combination of X-rays plus 2-AAPA were comparable to those from the combination of X-rays plus buthionine sulfoximine, a reference compound known to increase cancer sensitivity to radiation. The synergistic effect was correlated with an increase in cell thiol oxidative stress, which was reflected by a five-to sixfold increase in GSSG and 25% increase in total disulfides. No change in GSH or total thiols was observed as a result of GR inhibition.
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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.