ArticleBiochemical pharmacology2020
Cardiac glycosides inhibit cancer through Na/K-ATPase-dependent cell death induction.
Article in Biochemical pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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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.
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Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
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- Lanatoside C Inhibits Proliferation and Induces Apoptosis in Human Prostate Cancer Cells Through the TNF/IL-17 Signaling Pathway.International journal of molecular sciences · 2025Article
- Cardiac glycosides: Looking beyond heart failure and atrial fibrillation.Indian journal of pharmacology · 2025Article
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- Signature-based repurposed drugs resemble the inhibition of TGFβ-induced NDRG1 as potential therapeutics for triple-negative breast cancer.International journal of biological sciences · 2025Article
- Impacts of Senolytic Phytochemicals on Gut Microbiota: A Comprehensive Review.Journal of microbiology and biotechnology · 2024Review
- Drug Repurposing for Cancer Treatment: A Comprehensive Review.International journal of molecular sciences · 2024Review
- Combination of ethyl acetate fraction from Calotropis gigantea stem bark and sorafenib induces apoptosis in HepG2 cells.PloS one · 2024Article
- Transcriptome Profiling of Cardiac Glycoside Treatment Reveals EGR1 and Downstream Proteins of MAPK/ERK Signaling Pathway in Human Breast Cancer Cells.International journal of molecular sciences · 2023Article
- A novel sorbicillinoid compound as a potent anti-inflammation agent through inducing NLRP3 protein degradation.British journal of pharmacology · 2023Article
- MYO10 regulates genome stability and cancer inflammation through mediating mitosis.Cell reports · 2023Article
- Efforts in Bioprospecting Research: A Survey of Novel Anticancer Phytochemicals Reported in the Last Decade.Molecules (Basel, Switzerland) · 2022Review
- Synthesis and Biological Evaluation of Cardiac Glycosides for Cancer Therapy by Targeting the DNA Damage Response.ChemMedChem · 2022Article
- Monovalent ions and stress-induced senescence in human mesenchymal endometrial stem/stromal cells.Scientific reports · 2022Article
- Targeting metabolic reprogramming in chronic lymphocytic leukemia.Experimental hematology & oncology · 2022Review
- Oleandrin: A Systematic Review of its Natural Sources, Structural Properties, Detection Methods, Pharmacokinetics and Toxicology.Frontiers in pharmacology · 2022Review
- Glycosides for Peripheral Neuropathic Pain: A Potential Medicinal Components.Molecules (Basel, Switzerland) · 2021Review
- Emergence of Cardiac Glycosides as Potential Drugs: Current and Future Scope for Cancer Therapeutics.Biomolecules · 2021Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Successful drug repurposing relies on the understanding of molecular mechanisms of the target compound. Cardiac glycosides have demonstrated potent anticancer activities; however, the pharmacological mechanisms underlying their anticancer effects remained elusive, which has restricted their further development in cancer treatment. A bottleneck is the lack of comprehensive understanding about genes and signaling pathways that are altered at the early stage of drug treatment, which is key to understand how they inhibit cancer. To address this issue, we first investigated the anticancer effects of a panel of 68 naturally isolated cardiac glycosides. Our results illustrate critical structure activity relationship of these compounds on cancer cell survival. We confirmed the anticancer effect of cardiac glycoside in mouse tumor xenografts. Through RNA sequencing, quantitative PCR and immunoblotting, we show that cardiac glycoside first activated autophagy and then induced apoptosis. Further activating autophagy by rapamycin or inhibiting apoptosis by caspase inhibitor mitigated cardiac glycoside-induced cell death, whereas inhibiting autophagy by RNA interference-mediated depletion of critical autophagy genes enhanced cell death. While depletion of Na/K-ATPase, the protein target of cardiac glycosides, by RNA interference inhibited both autophagy activation and apoptosis induction by cardiac glycoside, expression of human, but not rodent Na/K-ATPase, increased cell sensitivity to cardiac glycoside. In conclusion, our analyses reveal sequential activation of autophagy and apoptosis during early stages of cardiac glycoside treatment and indicate the importance of Na/K-ATPase in their anticancer effects.
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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.