ArticleAging cell2021
Ouabain and chloroquine trigger senolysis of BRAF-V600E-induced senescent cells by targeting autophagy.
Article in Aging cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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
30 citing papers in PubMed, 47 citations in OpenAlex.
- Closing the gap in aging science: unlocking the potential of nanoparticles in senescence therapy.Biogerontology · 2026Review
- Insights into the therapeutic strategies for aging and aging-associated diseases.Signal transduction and targeted therapy · 2026Review
- Autophagy revealed as a targetable vulnerability in senescent cells by cell painting phenotypic profiling: a mechanistic study of MCOPPB and related compounds.GeroScience · 2026Article
- Morphofunctional Heterogeneity and Plasticity of Glioblastoma Cells Induced to Senescence by Temozolomide.Aging cell · 2026Article
- BRAF inhibitor resistance in melanoma: from resistance mechanisms to therapeutic innovations.Molecular biomedicine · 2026Review
- Emerging strategies in senotherapeutics: from broad-spectrum senolysis to precision reprogramming.npj aging · 2026Review
- Cleaning, Chasing and Calming: Promising Paradigms of Senotherapy in Aging-Related Diseases.International journal of biological sciences · 2026Review
- Unraveling the meta-hallmarks between senescent and tumor cells: A new perspective for senolytic drug discovery.Acta pharmaceutica Sinica. B · 2025Review
- Gut microbiota modulate intestinal inflammation by endoplasmic reticulum stress-autophagy-cell death signaling axis.Journal of animal science and biotechnology · 2025Review
- 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
- Article
- ATP1A1 is a promising new target for melanoma treatment and can be inhibited by its physiological ligand bufalin to restore targeted therapy efficacy.Cancer cell international · 2024Article
- Connecting epigenetics and inflammation in vascular senescence: state of the art, biomarkers and senotherapeutics.Frontiers in genetics · 2024Review
- Article
- Enhancement of Immunosuppressive Activity of Mesenchymal Stromal Cells by Platelet-Derived Factors is Accompanied by Apoptotic Priming.Stem cell reviews and reports · 2023Article
- Bioactive C21 Steroidal Glycosides fromMolecules (Basel, Switzerland) · 2023Article
- Multiple characteristic alterations and available therapeutic strategies of cellular senescence.Journal of Zhejiang University. Science. B · 2023Review
- Ulvophyte Green AlgaeMolecules (Basel, Switzerland) · 2023Article
- Cellular senescence in malignant cells promotes tumor progression in mouse and patient Glioblastoma.Nature communications · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The expression of BRAF-V600E triggers oncogene-induced senescence in normal cells and is implicated in the development of several cancers including melanoma. Here, we report that cardioglycosides such as ouabain are potent senolytics in BRAF senescence. Sensitization by ATP1A1 knockdown and protection by supplemental potassium showed that senolysis by ouabain was mediated by the Na,K-ATPase pump. Both ion transport inhibition and signal transduction result from cardioglycosides binding to Na,K-ATPase. An inhibitor of the pump that does not trigger signaling was not senolytic despite blocking ion transport, demonstrating that signal transduction is required for senolysis. Ouabain triggered the activation of Src, p38, Akt, and Erk in BRAF-senescent cells, and signaling inhibitors prevented cell death. The expression of BRAF-V600E increased ER stress and autophagy in BRAF-senescent cells and sensitized the cell to senolysis by ouabain. Ouabain inhibited autophagy flux, which was restored by signaling inhibitors. Consequently, we identified autophagy inhibitor chloroquine as a novel senolytic in BRAF senescence based on the mode of action of cardioglycosides. Our work underlies the interest of characterizing the mechanisms of senolytics to discover novel compounds and identifies the endoplasmic reticulum stress-autophagy tandem as a new vulnerability in BRAF senescence that can be exploited for the development of further senolytic strategies.
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.