ArticleCancers2020
Ouabain and Digoxin Activate the Proteasome and the Degradation of the ERα in Cells Modeling Primary and Metastatic Breast Cancer.
Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- Article
- The natural L370F ERα variant confers endocrine resistance and sensitivity to ATRA in metastatic breast cancer cells.Cell communication and signaling : CCS · 2026Article
- Overexpression of ATP1B2 promotes cancer cell migration and inhibits apoptosis in patients with esophageal squamous cell carcinoma.Oncology reports · 2025Article
- Targeting Ion Channels: Blockers Suppress Calcium Signals and Induce Cytotoxicity Across Medulloblastoma Cell Models.Bioengineering (Basel, Switzerland) · 2025Article
- Ouabain - a double-edged sword in tumor development and progression? a review of half a century.Frontiers in physiology · 2025Review
- Digoxin and its NaBioorganic & medicinal chemistry · 2024Review
- Selective impact of ALK and MELK inhibition on ERα stability and cell proliferation in cell lines representing distinct molecular phenotypes of breast cancer.Scientific reports · 2024Article
- Article
- Cardiac glycoside ouabain efficiently targets leukemic stem cell apoptotic machinery independent of cell differentiation status.Cell communication and signaling : CCS · 2023Article
- A functional genetic screen for metabolic proteins unveils GART and theFrontiers in endocrinology · 2023Article
- Timed use of digoxin prevents heart ischemia-reperfusion injury through a REV-ERBα-UPS signaling pathway.Nature cardiovascular research · 2022Article
- The antiviral drug telaprevir induces cell death by reducing FOXA1 expression in estrogen receptor α (ERα)-positive breast cancer cells.Molecular oncology · 2022Article
- Evaluation of the Sensitivity of Breast Cancer Cell Lines to Cardiac Glycosides Unveils ATP1B3 as a Possible Biomarker for the Personalized Treatment of ERα Expressing Breast Cancers.International journal of molecular sciences · 2022Article
- Clinically relevant CHK1 inhibitors abrogate wild-type and Y537S mutant ERα expression and proliferation in luminal primary and metastatic breast cancer cells.Journal of experimental & clinical cancer research : CR · 2022Article
- A New Anti-Estrogen Discovery Platform Identifies FDA-Approved Imidazole Anti-Fungal Drugs as Bioactive Compounds against ERα Expressing Breast Cancer Cells.International journal of molecular sciences · 2021Article
- Review
- Cardiac Glycoside Ouabain Exerts Anticancer ActivityFrontiers in oncology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Estrogen receptor α expressing breast cancers (BC) are classically treated with endocrine therapy. Prolonged endocrine therapy often results in a metastatic disease (MBC), for which a standardized effective therapy is still lacking. Thus, new drugs are required for primary and metastatic BC treatment. Here, we report that the Food and Drug Administration (FDA)-approved drugs, ouabain and digoxin, induce ERα degradation and prevent proliferation in cells modeling primary and metastatic BC. Ouabain and digoxin activate the cellular proteasome, instigating ERα degradation, which causes the inhibition of 17β-estradiol signaling, induces the cell cycle blockade in the G2 phase, and triggers apoptosis. Remarkably, these effects are independent of the inhibition of the Na/K pump. The antiproliferative effects of ouabain and digoxin occur also in diverse cancer models (i.e., tumor spheroids and xenografts). Additionally, gene profiling analysis reveals that these drugs downregulate the expression of genes related to endocrine therapy resistance. Therefore, ouabain and digoxin behave as 'anti-estrogen'-like drugs, and are appealing candidates for the treatment of primary and metastatic BCs.
Indexed as
Identifiers
What OpenQuestion holds
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.