ArticleBritish journal of cancer2021
Exploiting the reactive oxygen species imbalance in high-risk paediatric acute lymphoblastic leukaemia through auranofin.
Article in British journal of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 22 citations in OpenAlex.
- Pharmacological Insights: Mitochondrial ROS Generation by FNC (Azvudine) in Dalton's Lymphoma Cells Revealed by Super Resolution Imaging.Cell biochemistry and biophysics · 2024Article
- The thioredoxin system determines CHK1 inhibitor sensitivity via redox-mediated regulation of ribonucleotide reductase activity.Nature communications · 2024Article
- FDA-approved disulfiram as a novel treatment for aggressive leukemia.Journal of molecular medicine (Berlin, Germany) · 2024Article
- Auranofin Induces Lethality Driven by Reactive Oxygen Species in High-Grade Serous Ovarian Cancer Cells.Cancers · 2023Article
- Auranofin Synergizes with the PARP Inhibitor Olaparib to Induce ROS-Mediated Cell Death in Mutant p53 Cancers.Antioxidants (Basel, Switzerland) · 2023Article
- Combined thioredoxin reductase and glutaminase inhibition exerts synergistic anti-tumor activity in MYC-high high-grade serous ovarian carcinoma.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- The Gold(I) Complex with Plant Hormone Kinetin Shows Promising In Vitro Anticancer and PPARγ Properties.International journal of molecular sciences · 2023Article
- Menadione Potentiates Auranofin-Induced Glioblastoma Cell Death.International journal of molecular sciences · 2022Article
- Auranofin induces urothelial carcinoma cell death via reactive oxygen species production and synergy with cisplatin.Oncology letters · 2022Article
- The gold complex auranofin: new perspectives for cancer therapy.Discover oncology · 2021Review
- SystematicFrontiers in oncology · 2021Article
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe prognosis for high-risk childhood acute leukaemias remains dismal and established treatment protocols often cause long-term side effects in survivors. This study aims to identify more effective and safer therapeutics for these patients.
methodsA high-throughput phenotypic screen of a library of 3707 approved drugs and pharmacologically active compounds was performed to identify compounds with selective cytotoxicity against leukaemia cells followed by further preclinical evaluation in patient-derived xenograft models.
resultsAuranofin, an FDA-approved agent for the treatment of rheumatoid arthritis, was identified as exerting selective anti-cancer activity against leukaemia cells, including patient-derived xenograft cells from children with high-risk ALL, versus solid tumour and non-cancerous cells. It induced apoptosis in leukaemia cells by increasing reactive oxygen species (ROS) and potentiated the activity of the chemotherapeutic cytarabine against highly aggressive models of infant MLL-rearranged ALL by enhancing DNA damage accumulation. The enhanced sensitivity of leukaemia cells towards auranofin was associated with lower basal levels of the antioxidant glutathione and higher baseline ROS levels compared to solid tumour cells.
conclusionsOur study highlights auranofin as a well-tolerated drug candidate for high-risk paediatric leukaemias that warrants further preclinical investigation for application in high-risk paediatric and adult acute leukaemias.
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