ArticlePloS one2013
Human breast tumor cells are more resistant to cardiac glycoside toxicity than non-tumorigenic breast cells.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
25 citing papers in PubMed, 45 citations in OpenAlex.
- Article
- Na,K-ATPase mediated and cardiotonic induced signaling in health and disease.Frontiers in physiology · 2025Review
- Ouabain - a double-edged sword in tumor development and progression? a review of half a century.Frontiers in physiology · 2025Review
- Sensational site: the sodium pump ouabain-binding site and its ligands.American journal of physiology. Cell physiology · 2024Review
- Repurposing hyperpolarization-activated cyclic nucleotide-gated channels as a novel therapy for breast cancer.Clinical and translational medicine · 2021Article
- Bufalin attenuates triple-negative breast cancer cell stemness by inhibiting the expression of SOX2/OCT4.Oncology letters · 2020Article
- Article
- The sodium pump and digitalis drugs: Dogmas and fallacies.Pharmacology research & perspectives · 2019Review
- Review
- New therapeutic aspects of steroidal cardiac glycosides: the anticancer properties of Huachansu and its main active constituent Bufalin.Cancer cell international · 2019Review
- Recombinant expression of osmotin in barley improves stress resistance and food safety during adverse growing conditions.PloS one · 2019Article
- Divaricoside Exerts Antitumor Effects, in Part, by Modulating Mcl-1 in Human Oral Squamous Cell Carcinoma Cells.Computational and structural biotechnology journal · 2019Article
- Selective lysis of breast carcinomas by simultaneous stimulation of sodium channels and blockade of sodium pumps.Oncotarget · 2018Article
- Retinoschisin is linked to retinal Na/K-ATPase signaling and localization.Molecular biology of the cell · 2017Article
- Protein Interaction and Na/K-ATPase-Mediated Signal Transduction.Molecules (Basel, Switzerland) · 2017Review
- (+)-Strebloside-Induced Cytotoxicity in Ovarian Cancer Cells Is Mediated through Cardiac Glycoside Signaling Networks.Journal of natural products · 2017Article
- Protein Carbonylation of an Amino Acid Residue of the Na/K-ATPase α1 Subunit Determines Na/K-ATPase Signaling and Sodium Transport in Renal Proximal Tubular Cells.Journal of the American Heart Association · 2016Article
- The Role of Na/K-ATPase Signaling in Oxidative Stress Related to Obesity and Cardiovascular Disease.Molecules (Basel, Switzerland) · 2016Review
- Do Src Kinase and Caveolin Interact Directly with Na,K-ATPase?The Journal of biological chemistry · 2016Article
- Regulation of Cardiac Remodeling by Cardiac Na(+)/K(+)-ATPase Isoforms.Frontiers in physiology · 2016Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Cardiotonic steroids (CTS), specific inhibitors of Na,K-ATPase activity, have been widely used for treating cardiac insufficiency. Recent studies suggest that low levels of endogenous CTS do not inhibit Na,K-ATPase activity but play a role in regulating blood pressure, inducing cellular kinase activity, and promoting cell viability. Higher CTS concentrations inhibit Na,K-ATPase activity and can induce reactive oxygen species, growth arrest, and cell death. CTS are being considered as potential novel therapies in cancer treatment, as they have been shown to limit tumor cell growth. However, there is a lack of information on the relative toxicity of tumor cells and comparable non-tumor cells. We have investigated the effects of CTS compounds, ouabain, digitoxin, and bufalin, on cell growth and survival in cell lines exhibiting the full spectrum of non-cancerous to malignant phenotypes. We show that CTS inhibit membrane Na,K-ATPase activity equally well in all cell lines tested regardless of metastatic potential. In contrast, the cellular responses to the drugs are different in non-tumor and tumor cells. Ouabain causes greater inhibition of proliferation and more extensive apoptosis in non-tumor breast cells compared to malignant or oncogene-transfected cells. In tumor cells, the effects of ouabain are accompanied by activation of anti-apoptotic ERK1/2. However, ERK1/2 or Src inhibition does not sensitize tumor cells to CTS cytotoxicity, suggesting that other mechanisms provide protection to the tumor cells. Reduced CTS-sensitivity in breast tumor cells compared to non-tumor cells indicates that CTS are not good candidates as cancer 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.