ArticleOncoTargets and therapy2021
Ouabain Exhibited Strong Anticancer Effects in Melanoma Cells via Induction of Apoptosis, G2/M Phase Arrest, and Migration Inhibition.
Article in OncoTargets and therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
- Steroidal Compounds at the Crossroads of Inflammation and Cancer: Implications for Drug Discovery and Therapy.Biomedicines · 2026Review
- Cardiac Glycosides: From Natural Defense Molecules to Emerging Therapeutic Agents.Biomolecules · 2025Review
- Ouabain - a double-edged sword in tumor development and progression? a review of half a century.Frontiers in physiology · 2025Review
- From hormonal immunomodulation to glioblastoma therapy: the emerging role of Ouabain.Frontiers in immunology · 2025Review
- Digoxin and its NaBioorganic & medicinal chemistry · 2024Review
- The cardiac glycoside ZINC253504760 induces parthanatos-type cell death and G2/M arrest via downregulation of MEK1/2 phosphorylation in leukemia cells.Cell biology and toxicology · 2023Article
- Mesenchymal Stem/Stromal Cells in Three-Dimensional Cell Culture: Ion Homeostasis and Ouabain-Induced Apoptosis.Biomedicines · 2023Article
- The Role of Senescent Cells in Acquired Drug Resistance and Secondary Cancer in BRAFi-Treated Melanoma.Cancers · 2021Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMalignant melanoma was characterized by insensitive chemotherapy, drug resistance, and high metastatic ability, which resulted in the main reason for the mortality among skin-related cancers. The current agents were not sufficient to improve the treatment status of melanoma patients, and it was still needed to develop new chemotherapeutic drugs for melanoma. Our study aimed to study the anticancer effects and potential mechanisms of ouabain on melanoma cells.
methodsThe inhibitory effects of ouabain were determined by CCK8 and colony formation assays, and the morphological changes of melanoma cells were observed by inverted microscope. The apoptosis induction and cell cycle distribution were detected by annexin V/PI double staining and PI staining, respectively. The expression of the biomarker proteins in apoptosis and G2/M phase were determined by Western blotting analysis. The effects of ouabain on the migration of melanoma cells were measured by transwell migration assay and wound closure analysis. The potential mechanisms of ouabain in melanoma cells were analyzed by transcriptome sequencing.
resultsOur present study demonstrated that ouabain exhibited strong inhibitory effects on cell proliferation and triggered dramatical morphological changes of melanoma cells. Moreover, ouabain induced significant apoptosis in A375 rather than SK-Mel-28 cells via upregulation of bax expression and downregulation of bcl-2 expression. Consistently, ouabain treatment induced cell cycle arrest at G2/M phase in both A375 and SK-Mel-28 cells via upregulation of cyclin B1 and downregulation of cdc2 and cdc25c. Importantly, ouabain suppressed the migration of A375 and SK-Mel-28 cells. Furthermore, the transcriptome sequencing demonstrated that p53 and MAPK signaling pathway might play important roles in the inhibitory effects of ouabain.
conclusionOur study revealed that ouabain exhibited dramatical anticancer effects, which provided a novel application for cardiac glycoside drugs in the clinical treatment of melanoma.
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