ArticleOncotarget2017
Cardiac glycosides suppress the maintenance of stemness and malignancy via inhibiting HIF-1α in human glioma stem cells.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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.
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
21 citing papers in PubMed, 39 citations in OpenAlex.
- Cardiac Glycosides: From Natural Defense Molecules to Emerging Therapeutic Agents.Biomolecules · 2025Review
- Digitoxose as powerful glycosyls for building multifarious glycoconjugates of natural products and un-natural products.Synthetic and systems biotechnology · 2024Review
- Interconnection of CD133 Stem Cell Marker with Autophagy and Apoptosis in Colorectal Cancer.International journal of molecular sciences · 2024Review
- PBI-05204, a supercritical CONeoplasia (New York, N.Y.) · 2024Article
- Understanding the Significance of Hypoxia-Inducible Factors (HIFs) in Glioblastoma: A Systematic Review.Cancers · 2024Review
- The mechanistic role of cardiac glycosides in DNA damage response and repair signaling.Cellular and molecular life sciences : CMLS · 2023Review
- Review
- Digitoxin Affects Metabolism, ROS Production and Proliferation in Pancreatic Cancer Cells Differently Depending on the Cell Phenotype.International journal of molecular sciences · 2022Article
- Repurposing Cardiac Glycosides: Drugs for Heart Failure Surmounting Viruses.Molecules (Basel, Switzerland) · 2021Review
- Emergence of Cardiac Glycosides as Potential Drugs: Current and Future Scope for Cancer Therapeutics.Biomolecules · 2021Review
- Review
- NaMolecules (Basel, Switzerland) · 2021Review
- Hypoxia-induced therapy resistance: Available hypoxia-targeting strategies and current advances in head and neck cancer.Translational oncology · 2021Review
- The Multifaceted Role of CMA in Glioma: Enemy or Ally?International journal of molecular sciences · 2021Review
- Glioma stem cells and their roles within the hypoxic tumor microenvironment.Theranostics · 2021Review
- Digitoxin inhibits proliferation of multidrug-resistant HepG2 cells through GOncology letters · 2020Article
- A multiplexed bioluminescent reporter for sensitive and non-invasive tracking of DNA double strand break repair dynamics in vitro and in vivo.Nucleic acids research · 2020Article
- Dexamethasone inhibits stemness maintenance and enhances chemosensitivity of hepatocellular carcinoma stem cells by inducing deSUMOylation of HIF‑1α and Oct4.International journal of oncology · 2020Article
- Anticancer and Antiviral Properties of Cardiac Glycosides: A Review to Explore the Mechanism of Actions.Molecules (Basel, Switzerland) · 2020Review
- The Botanical Drug PBI-05204, a Supercritical COFrontiers in pharmacology · 2020Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Tissue hypoxia contributes to solid tumor pathogenesis by activating a series of adaptive programs. We previously showed that hypoxia promotes the preferential expansion and maintenance of CD133 positive human glioma stem cells (GSC) in a hypoxia inducible factor 1 alpha (HIF-1α)-dependent mechanism. Here, we examined the activity of digitoxin (DT), a cardiac glycoside and a putative inhibitor of HIF-1α, on human GSC in vitro and in vivo. During hypoxic conditions (1% O2), we observed the effect of DT on the intracellular level of HIF-1α and the extracellular level of vascular endothelial growth factor (VEGF) in human GSC. We found that DT at clinically achievable concentrations, suppressed HIF-1α accumulation during hypoxic conditions in human GSC and established glioma cell lines. DT treatment also significantly attenuated hypoxia-induced expression of VEGF, a downstream target of HIF-1α. Exposure to DT also reduced hypoxia-induced activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway. Furthermore, DT potently inhibited neurosphere formation, and decreased CD133 expression even at concentrations that were not overtly cytotoxic. Lastly, treatment with DT reduced GSC engraftment in an in vivo xenograft model of glioblastoma. Intraperitoneal injections of DT significantly inhibited the growth of established glioblastoma xenografts, and suppressed expression of HIF-1α and carbonic anhydrase (CA9), a surrogate marker of hypoxia. Taken together, these results suggest that DT at clinically achievable concentration functions as an inhibitor of HIF-1α, worthy of further investigations in the therapy of glioblastoma.
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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.