ArticleOncotarget2018
Synthetic lethality of the ALDH3A1 inhibitor dyclonine and xCT inhibitors in glutathione deficiency-resistant cancer cells.
Article in Oncotarget, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.
- Ferroptosis in chemotherapy resistance and resensitization in breast cancer: a systematic review of preclinical evidence and translational implications.Frontiers in oncology · 2026Pooled it
- Metab8D: a metabolic regulome network from multiomics and machine learning.Communications biology · 2026Article
- Drug Repurposing Screen Identifies Pimozide as a ROS-Inducing Therapy With Anti-Tumor Efficacy in HNSCC PDX Models.Cancer science · 2026Article
- YAP1 depletion enhances TAZ and its complexation with TEAD4 and AP-1 heterodimer C-JUN/FOSB in gastric cancer progression and metastasis.Cancer heterogeneity and plasticity · 2026Article
- DCF-resistant ESCC redevelops drug sensitivity when combined with calcium channel blockers due to ER stress response.Esophagus : official journal of the Japan Esophageal Society · 2025Article
- CD44: a key regulator of iron metabolism, redox balance, and therapeutic resistance in cancer stem cells.Stem cells (Dayton, Ohio) · 2025Review
- HSP90 inhibitor AUY922 suppresses tumor growth and modulates immune response through YAP1-TEAD pathway inhibition in gastric cancer.Cancer letters · 2025Article
- Pharmacogenomic screening identifies and repurposes leucovorin and dyclonine as pro-oligodendrogenic compounds in brain repair.Nature communications · 2024Article
- Identification of Novel Isatin Derivative Bearing a Nitrofuran Moiety as Potent Multi-Isoform Aldehyde Dehydrogenase Inhibitor.Molecules (Basel, Switzerland) · 2024Article
- Lipid-derived electrophiles inhibit the function of membrane channels during ferroptosis.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Informed by Cancer Stem Cells of Solid Tumors: Advances in Treatments Targeting Tumor-Promoting Factors and Pathways.International journal of molecular sciences · 2024Review
- Review
- Ferroptosis in head and neck squamous cell carcinoma: from pathogenesis to treatment.Frontiers in pharmacology · 2024Review
- Galectin-3 Cooperates with CD47 to Suppress Phagocytosis and T-cell Immunity in Gastric Cancer Peritoneal Metastases.Cancer research · 2023Article
- NRF2, a Superstar of Ferroptosis.Antioxidants (Basel, Switzerland) · 2023Review
- Human Aldehyde Dehydrogenases: A Superfamily of Similar Yet Different Proteins Highly Related to Cancer.Cancers · 2023Review
- Inhibition of lung adenocarcinoma by combinations of sulfasalazine (SAS) and disulfiram-copper (DSF-Cu) in cell line models and mice.Carcinogenesis · 2023Article
- Advances in the study of regulators of ferroptosis in head and neck squamous cell carcinoma (Review).International journal of molecular medicine · 2023Review
- Molecular Mechanisms of Ferroptosis and Updates of Ferroptosis Studies in Cancers and Leukemia.Cells · 2023Review
- Aldehyde dehydrogenase in solid tumors and other diseases: Potential biomarkers and therapeutic targets.MedComm · 2023Review
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cystine-glutamate antiporter subunit xCT suppresses iron-dependent oxidative cell death (ferroptosis) and is therefore a promising target for cancer treatment. Given that cancer cells often show resistance to xCT inhibition resulting in glutathione (GSH) deficiency, however, we here performed a synthetic lethal screen of a drug library to identify agents that sensitize the GSH deficiency-resistant cancer cells to the xCT inhibitor sulfasalazine. This screen identified the oral anesthetic dyclonine which has been recently reported to act as a covalent inhibitor for aldehyde dehydrogenases (ALDHs). Treatment with dyclonine induced intracellular accumulation of the toxic aldehyde 4-hydroxynonenal in a cooperative manner with sulfasalazine. Sulfasalazine-resistant head and neck squamous cell carcinoma (HNSCC) cells were found to highly express ALDH3A1 and knockdown of ALDH3A1 rendered these cells sensitive to sulfasalazine. The combination of dyclonine and sulfasalazine cooperatively suppressed the growth of highly ALDH3A1-expressing HNSCC or gastric tumors that were resistant to sulfasalazine monotherapy. Our findings establish a rationale for application of dyclonine as a sensitizer to xCT-targeted cancer therapy.
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