ArticleProceedings of the National Academy of Sciences of the United States of America2004
Digitoxin mimics gene therapy with CFTR and suppresses hypersecretion of IL-8 from cystic fibrosis lung epithelial cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 98 citations in OpenAlex.
- Digitoxin for Airway Inflammation in Cystic Fibrosis: Preliminary Assessment of Safety, Pharmacokinetics, and Dose Finding.Annals of the American Thoracic Society · 2017Trial
- PM2.5 toxin benzo[a]pyrene induces life-limiting inflammation and oxidative stress in the airway by up-regulation of TRPC6 and inactivation of β2AR/CFTR signaling.bioRxiv : the preprint server for biology · 2026Article
- Inflammation in the COVID-19 airway is due to inhibition of CFTR signaling by the SARS-CoV-2 spike protein.Scientific reports · 2024Article
- The modulation of immune cell death in connection to microRNAs and natural products.Frontiers in immunology · 2024Review
- A cytochrome P450 CYP87A4 imparts sterol side-chain cleavage in digoxin biosynthesis.Nature communications · 2023Article
- Human pluripotent stem cell-derived macrophages host Mycobacterium abscessus infection.Stem cell reports · 2022Article
- Common cardiac medications potently inhibit ACE2 binding to the SARS-CoV-2 Spike, and block virus penetration and infectivity in human lung cells.Scientific reports · 2021Article
- NaFrontiers in pharmacology · 2021Review
- Gene therapy-emulating small molecule treatments in cystic fibrosis airway epithelial cells and patients.Respiratory research · 2019Article
- Digitoxin Inhibits Epithelial-to-Mesenchymal-Transition in Hereditary Castration Resistant Prostate Cancer.Frontiers in oncology · 2019Article
- Cyclin E and FGF8 are downstream cell growth regulators in distinct tumor suppressor effects of ANXA7 in hormone-resistant cancer cells of breast versus prostate origin.Trends in cancer research · 2018Article
- Drug-set enrichment analysis: a novel tool to investigate drug mode of action.Bioinformatics (Oxford, England) · 2016Article
- CFTR Controls the Activity of NF-κB by Enhancing the Degradation of TRADD.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2016Article
- Activation of 3-phosphoinositide-dependent kinase 1 (PDK1) and serum- and glucocorticoid-induced protein kinase 1 (SGK1) by short-chain sphingolipid C4-ceramide rescues the trafficking defect of ΔF508-cystic fibrosis transmembrane conductance regulator (ΔF508-CFTR).The Journal of biological chemistry · 2014Article
- Realizing the promise of reverse phase protein arrays for clinical, translational, and basic research: a workshop report: the RPPA (Reverse Phase Protein Array) society.Molecular & cellular proteomics : MCP · 2014Article
- Cellular location and expression of Na+, K+ -ATPase α subunits affect the anti-proliferative activity of oleandrin.Molecular carcinogenesis · 2014Article
- Cardiac glycosides in cancer therapy: from preclinical investigations towards clinical trials.Investigational new drugs · 2013Review
- Digitoxin induces apoptosis in cancer cells by inhibiting nuclear factor of activated T-cells-driven c-MYC expression.Journal of carcinogenesis · 2013Article
- Digitoxin and its analogs as novel cancer therapeutics.Experimental hematology & oncology · 2012Article
- Influence of interleukin-8 (IL-8) and IL-8 receptors on the migration of human keratinocytes, the role of PLC-γ and potential clinical implications.Experimental and therapeutic medicine · 2012Article
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Cystic fibrosis (CF) is a fatal, autosomal, recessive genetic disease that is characterized by profound lung inflammation. The inflammatory process is believed to be caused by massive overproduction of the proinflammatory protein IL-8, and the high levels of IL-8 in the CF lung are therefore believed to be the central mechanism behind CF lung pathophysiology. We show here that digitoxin, at sub nM concentrations, can suppress hypersecretion of IL-8 from cultured CF lung epithelial cells. Certain other cardiac glycosides are also active but with much less potency. The specific mechanism of digitoxin action is to block phosphorylation of the inhibitor of NF-kappa B (I kappa B alpha). I kappa B alpha phosphorylation is a required step in the activation of the NF-kappa B signaling pathway and the subsequent expression of IL-8. Digitoxin also has effects on global gene expression in CF cells. Of the informative genes expressed by the CF epithelial cell line IB-3, 58 are significantly (P < 0.05) affected by gene therapy with wild-type (CFTR CF transmembrane conductance regulator). Of these 58 genes, 36 (62%) are similarly affected by digitoxin and related active analogues. We interpret this result to suggest that digitoxin can also partially mimic the genomic consequences of gene therapy with CF transmembrane conductance regulator. We therefore suggest that digitoxin, with its lengthy history of human use, deserves consideration as a candidate drug for suppressing IL-8-dependent lung inflammation in CF.
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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.