ArticleJournal of carcinogenesis2013
Digitoxin induces apoptosis in cancer cells by inhibiting nuclear factor of activated T-cells-driven c-MYC expression.
Article in Journal of carcinogenesis, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 25 citations in OpenAlex.
- Intron Retention of DDX39A Driven by SNRPD2 is a Crucial Splicing Axis for Oncogenic MYC/Spliceosome Program in Hepatocellular Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Cardiac glycoside ouabain efficiently targets leukemic stem cell apoptotic machinery independent of cell differentiation status.Cell communication and signaling : CCS · 2023Article
- Cytotoxic effect of carbohydrate derivatives of digitoxigenin involves modulation of plasma membrane CaJournal of cellular biochemistry · 2021Article
- Digitoxin inhibits proliferation of multidrug-resistant HepG2 cells through GOncology letters · 2020Article
- Heart failure drug proscillaridin A targets MYC overexpressing leukemia through global loss of lysine acetylation.Journal of experimental & clinical cancer research : CR · 2019Article
- Tracing MYC Expression for Small Molecule Discovery.Cell chemical biology · 2019Article
- Digitoxin Inhibits Epithelial-to-Mesenchymal-Transition in Hereditary Castration Resistant Prostate Cancer.Frontiers in oncology · 2019Article
- Revisiting the Concept of Targeting NFAT to Control T Cell Immunity and Autoimmune Diseases.Frontiers in immunology · 2018Review
- Searching for the Chokehold of NRAS Mutant Melanoma.The Journal of investigative dermatology · 2016Review
- Inhibiting NFAT1 for breast cancer therapy: New insights into the mechanism of action of MDM2 inhibitor JapA.Oncotarget · 2015Article
- Exposure to 3G mobile phone signals does not affect the biological features of brain tumor cells.BMC public health · 2015Article
- NFAT as cancer target: mission possible?Biochimica et biophysica acta · 2014Review
- NaMedicine internationalArticle
- Classical Drug Digitoxin Inhibits Influenza Cytokine Storm, With Implications for Covid-19 Therapy.In vivo (Athens, Greece)Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundCardiac glycosides such as digitoxin have been shown to directly cause apoptotic death of cancer cells both in vitro, and in vivo. However, the mechanism connecting cardiac glycoside action to apoptosis is not known. It has been reported that compounds resembling digitoxin are able to reduce c-MYC expression. Furthermore, it has been previously shown that the transcription of c-MYC depends on nuclear factor of activated T-cells (NFAT) binding sites in the c-MYC promoter. We have therefore hypothesized that NFAT might mediate digitoxin effects on c-MYC mRNA message. MATERIALS AND
methodsWe have chosen to study this process in HeLa cells where structurally intact c-MYC genes in 8q24 co-localize with human papilloma virus 18 at all integration sites.
resultsHere we show that within the 1(st) h following treatment with digitoxin, a significant reduction in c-MYC mRNA occurs. This is followed by a precipitous loss of c-MYC protein, activation of caspase 3, and subsequent apoptotic cell death. To test the NFAT-dependence mechanism, we analyzed the effects of digitoxin on NFAT isoform-dependent auto-activation of a NFAT-luciferase expression system. Drug dependent effects on expression varied according to each of the four canonical NFAT isoforms (1, 2, 3 or 4). The most digitoxin-sensitive NFAT isoform was NFAT1. Using c-MYC chromatin immune precipitation, we find that digitoxin inhibits interaction of NFAT1 with the proximal c-MYC promoter.
conclusionsThese results suggest that the carcinotoxic activity of digitoxin includes suppression of NFAT-driven c-MYC expression.
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