ArticleBritish journal of cancer2012
Quiescence and γH2AX in neuroblastoma are regulated by ouabain/Na,K-ATPase.
Article in British journal of cancer, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 32 citations in OpenAlex.
- From hormonal immunomodulation to glioblastoma therapy: the emerging role of Ouabain.Frontiers in immunology · 2025Review
- In Vitro Study of the Multimodal Effect of NaBiomedicines · 2023Article
- A novel method for generating glutamatergic SH-SY5Y neuron-like cells utilizing B-27 supplement.Frontiers in pharmacology · 2022Article
- The Most Competent Plant-Derived Natural Products for Targeting Apoptosis in Cancer Therapy.Biomolecules · 2021Review
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- Steroid Glycosides Hyrcanoside and Deglucohyrcanoside: On Isolation, Structural Identification, and Anticancer Activity.Foods (Basel, Switzerland) · 2021Article
- Integrative proteomic and functional analyses provide novel insights into the action of the repurposed drug candidate nitroxoline in AsPC-1 cells.Scientific reports · 2020Article
- Modular Total Synthesis and Cell-Based Anticancer Activity Evaluation of Ouabagenin and Other Cardiotonic Steroids with Varying Degrees of Oxygenation.Journal of the American Chemical Society · 2019Article
- Na/K Pump and Beyond: Na/K-ATPase as a Modulator of Apoptosis and Autophagy.Molecules (Basel, Switzerland) · 2017Review
- Synergistic effects of ion transporter and MAP kinase pathway inhibitors in melanoma.Nature communications · 2016Article
- Analysis of proliferation and apoptotic induction by 20 steroid glycosides in 143B osteosarcoma cells in vitro.Cell proliferation · 2015Article
- Two preclinical tests to evaluate anticancer activity and to help validate drug candidates for clinical trials.Oncoscience · 2015Article
- The in vivo antitumor activity of cardiac glycosides in mice xenografted with human cancer cells is probably an experimental artifact.Oncogene · 2014Article
- Article
- Evaluating the cancer therapeutic potential of cardiac glycosides.BioMed research international · 2014Review
- Neuroblastoma: developmental biology, cancer genomics and immunotherapy.Nature reviews. Cancer · 2013Review
- Comment on 'Quiescence and γH2AX in neuroblastoma are regulated by ouabain/Na,K-ATPase': ouabain and cancer.British journal of cancer · 2013Article
- Reply: Comment on 'Quiescence and yH2AX in neuroblastoma are regulated by ouabain/Na,K-ATPase': ouabain and cancer.British journal of cancer · 2013Article
- Ouabain, a cardiac glycoside, inhibits the Fanconi anemia/BRCA pathway activated by DNA interstrand cross-linking agents.PloS one · 2013Article
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Authors and funding
13 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCellular quiescence is a state of reversible proliferation arrest that is induced by anti-mitogenic signals. The endogenous cardiac glycoside ouabain is a specific ligand of the ubiquitous sodium pump, Na,K-ATPase, also known to regulate cell growth through unknown signalling pathways.
methodsTo investigate the role of ouabain/Na,K-ATPase in uncontrolled neuroblastoma growth we used xenografts, flow cytometry, immunostaining, comet assay, real-time PCR, and electrophysiology after various treatment strategies.
resultsThe ouabain/Na,K-ATPase complex induced quiescence in malignant neuroblastoma. Tumour growth was reduced by >50% when neuroblastoma cells were xenografted into immune-deficient mice that were fed with ouabain. Ouabain-induced S-G2 phase arrest, activated the DNA-damage response (DDR) pathway marker γH2AX, increased the cell cycle regulator p21(Waf1/Cip1) and upregulated the quiescence-specific transcription factor hairy and enhancer of split1 (HES1), causing neuroblastoma cells to ultimately enter G0. Cells re-entered the cell cycle and resumed proliferation, without showing DNA damage, when ouabain was removed.
conclusionThese findings demonstrate a novel action of ouabain/Na,K-ATPase as a regulator of quiescence in neuroblastoma, suggesting that ouabain can be used in chemotherapies to suppress tumour growth and/or arrest cells to increase the therapeutic index in combination therapies.
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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.