ArticlePloS one2014
HERG K+ channel-dependent apoptosis and cell cycle arrest in human glioblastoma cells.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 53 citations in OpenAlex.
- Comparative Interactome Analysis Reveals Architectural Principles Governing KInternational journal of molecular sciences · 2026Article
- Review
- Apoptotic and senolytic effects of hERG/Eag1 channel blockers in combination with temozolomide in human glioblastoma cells.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Biophysical Properties of Somatic Cancer Mutations in the S4 Transmembrane Segment of the Human Voltage-Gated Proton Channel hHBiomolecules · 2025Article
- Novel insights into voltage-gated ion channels: Translational breakthroughs in medical oncology.Channels (Austin, Tex.) · 2024Article
- Article
- hERG channel agonist NS1643 strongly inhibits invasive astrocytoma cell line SMA-560.PloS one · 2024Article
- Effect of THz Waves of Different Orientations on KInternational journal of molecular sciences · 2023Article
- Ion Channels in Gliomas-From Molecular Basis to Treatment.International journal of molecular sciences · 2023Review
- Review
- Mechanisms of Cell Cycle Arrest and Apoptosis in Glioblastoma.Biomedicines · 2022Review
- Potassium Channels as a Target for Cancer Therapy: Current Perspectives.OncoTargets and therapy · 2022Review
- Letrozole targets the human ether-a-go-go-related gene potassium current in glioblastoma.Basic & clinical pharmacology & toxicology · 2021Article
- Kcnh2 mediates FAK/AKT-FOXO3A pathway to attenuate sepsis-induced cardiac dysfunction.Cell proliferation · 2021Article
- Review
- Article
- Voltage-Gated Potassium Channels as Regulators of Cell Death.Frontiers in cell and developmental biology · 2020Review
- Voltage-Gated KFrontiers in pharmacology · 2020Review
- Dual effects of arsenic trioxide on tumor cells and the potential underlying mechanisms.Oncology letters · 2018Article
- Reactive Astrocytes in Glioblastoma Multiforme.Molecular neurobiology · 2018Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glioblastoma (GB) is associated with poor patient survival owing to uncontrolled tumor proliferation and resistance to apoptosis. Human ether-a-go-go-related gene K(+) channels (hERG; Kv11.1, KCNH2) are expressed in multiple cancer cells including GB and control cell proliferation and death. We hypothesized that pharmacological targeting of hERG protein would inhibit tumor growth by inducing apoptosis of GB cells. The small molecule hERG ligand doxazosin induced concentration-dependent apoptosis of human LNT-229 (EC50 = 35 µM) and U87MG (EC50 = 29 µM) GB cells, accompanied by cell cycle arrest in the G0/G1 phase. Apoptosis was associated with 64% reduction of hERG protein. HERG suppression via siRNA-mediated knock down mimicked pro-apoptotic effects of doxazosin. Antagonism of doxazosin binding by the non-apoptotic hERG ligand terazosin resulted in rescue of protein expression and in increased survival of GB cells. At the molecular level doxazosin-dependent apoptosis was characterized by activation of pro-apoptotic factors (phospho-erythropoietin-producing human hepatocellular carcinoma receptor tyrosine kinase A2, phospho-p38 mitogen-activated protein kinase, growth arrest and DNA damage inducible gene 153, cleaved caspases 9, 7, and 3), and by inactivation of anti-apoptotic poly-ADP-ribose-polymerase, respectively. In summary, this work identifies doxazosin as small molecule compound that promotes apoptosis and exerts anti-proliferative effects in human GB cells. Suppression of hERG protein is a crucial molecular event in GB cell apoptosis. Doxazosin and future derivatives are proposed as novel options for more effective GB treatment.
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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.