ArticleCancer science2020
Vasodilator oxyfedrine inhibits aldehyde metabolism and thereby sensitizes cancer cells to xCT-targeted therapy.
Article in Cancer science, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Ferroptosis as a Translational Axis in Small Cell Lung Cancer: A Systematic Review of Redox Pathways and Precision Oncology Prospects.Oncology research · 2026Pooled it
- A ferroptosis-suppressive state drives resistance to bladder-preserving chemoradiotherapy in muscle-invasive bladder cancer.Signal transduction and targeted therapy · 2026Article
- TGF-β Enhances Doxorubicin Resistance and Anchorage-Independent Growth in Cancer Cells by Inducing ALDH1A1 Expression.Cancer science · 2025Article
- CD44: a key regulator of iron metabolism, redox balance, and therapeutic resistance in cancer stem cells.Stem cells (Dayton, Ohio) · 2025Review
- xCT as a potential marker for neuroendocrine cells in high-risk prostate cancer and the relation to AL122023.1-miR-26a/30d/30e axis.PloS one · 2025Article
- Current advances on the role of ferroptosis in tumor immune evasion.Discover oncology · 2024Review
- Zinc oxide nanoparticles mitigate the malignant progression of ovarian cancer by mediating autophagy-dependent ferroptosis.Journal of cancer research and clinical oncology · 2024Article
- Targeting ferroptosis opens new avenues for the development of novel therapeutics.Signal transduction and targeted therapy · 2023Review
- Molecular Mechanisms of Ferroptosis and Updates of Ferroptosis Studies in Cancers and Leukemia.Cells · 2023Review
- Metabolic regulation of ferroptosis in the tumor microenvironment.The Journal of biological chemistry · 2022Review
- System XcInvestigational new drugs · 2021Review
- Targeting NRF2 to suppress ferroptosis in brain injury.Histology and histopathology · 2021Review
- Total body irradiation causes a chronic decrease in antioxidant levels.Scientific reports · 2021Article
- Review
- Sulfasalazine Sensitizes Polyhematoporphyrin-Mediated Photodynamic Therapy in Cholangiocarcinoma by Targeting xCT.Frontiers in pharmacology · 2021Article
- Ferroptosis in Cancer Treatment: Another Way to Rome.Frontiers in oncology · 2020Review
- SLC7A11/xCT in cancer: biological functions and therapeutic implications.American journal of cancer research · 2020Review
- Vasodilator oxyfedrine inhibits aldehyde metabolism and thereby sensitizes cancer cells to xCT-targeted therapy.Cancer science · 2020Article
- Radiation-induced alterations in the cancer microenvironment (Review).Medicine internationalReview
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The major cellular antioxidant glutathione (GSH) protects cancer cells from oxidative damage that can lead to the induction of ferroptosis, an iron-dependent form of cell death triggered by the aberrant accumulation of lipid peroxides. Inhibitors of the cystine-glutamate antiporter subunit xCT, which mediates the uptake of extracellular cystine and thereby promotes GSH synthesis, are thus potential anticancer agents. However, the efficacy of xCT-targeted therapy has been found to be diminished by metabolic reprogramming that affects redox status in cancer cells. Identification of drugs for combination with xCT inhibitors that are able to overcome resistance to xCT-targeted therapy might thus provide the basis for effective cancer treatment. We have now identified the vasodilator oxyfedrine (OXY) as a sensitizer of cancer cells to GSH-depleting agents including the xCT inhibitor sulfasalazine (SSZ). Oxyfedrine contains a structural motif required for covalent inhibition of aldehyde dehydrogenase (ALDH) enzymes, and combined treatment with OXY and SSZ was found to induce accumulation of the cytotoxic aldehyde 4-hydroxynonenal and cell death in SSZ-resistant cancer cells both in vitro and in vivo. Microarray analysis of tumor xenograft tissue showed cyclooxygenase-2 expression as a potential biomarker for the efficacy of such combination therapy. Furthermore, OXY-mediated ALDH inhibition was found to sensitize cancer cells to GSH depletion induced by radiation therapy in vitro. Our findings thus establish a rationale for repurposing of OXY as a sensitizing drug for cancer treatment with agents that induce GSH depletion.
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Registered trials
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