ArticleEMBO molecular medicine2012
Inhibitors of mitochondrial Kv1.3 channels induce Bax/Bak-independent death of cancer cells.
Article in EMBO molecular medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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Who cites it
95 citing papers in PubMed, 164 citations in OpenAlex.
- Potassium channels in cancer: from hallmarks to therapeutic targeting.Journal of physiology and biochemistry · 2026Review
- Mitochondria-Targeting Moieties Based on N-Tethered Pyridinium Cations.Angewandte Chemie (International ed. in English) · 2026Article
- Investigating the Effects of Sea Anemone (Stichodactyla haddoni) Toxin on Potassium and Sodium Channel Gene Expression and Cell Death Mechanisms in A549 Cells.Marine biotechnology (New York, N.Y.) · 2026Article
- Reliable high-PAP-1-loaded polymeric micelles for cancer therapy: preparation, characterization, and evaluation of anti-tumor efficacy.Drug delivery · 2025Article
- Selective inhibition of mitochondrial Kv1.3 prevents and alleviates multiple sclerosis in vivo.EMBO molecular medicine · 2025Article
- Inhibition of HCN Channels Enhances Oxidative Stress and Autophagy of NRK-52E Cells Under NHInternational journal of molecular sciences · 2025Article
- Cannabidiol Enhances Stress-Induced Cellular Damage: Potential Contribution of Kv2.1 Inhibition.Journal of molecular neuroscience : MN · 2025Article
- Role of Sphingosine-1-Phosphate Signaling Pathway in Pancreatic Diseases.International journal of molecular sciences · 2024Review
- BioID-based intact cell interactome of the Kv1.3 potassium channel identifies a Kv1.3-STAT3-p53 cellular signaling pathway.Science advances · 2024Article
- Sphingosine is involved in PAPTP-induced death of pancreas cancer cells by interfering with mitochondrial functions.Journal of molecular medicine (Berlin, Germany) · 2024Article
- Advances in the role of ion channels in leukemia.Heliyon · 2024Review
- Loss of the large conductance calcium-activated potassium channel causes an increase in mitochondrial reactive oxygen species in glioblastoma cells.Pflugers Archiv : European journal of physiology · 2023Article
- The Phosphorylation of Kv1.3: A Modulatory Mechanism for a Multifunctional Ion Channel.Cancers · 2023Review
- Potassium Channels, Glucose Metabolism and Glycosylation in Cancer Cells.International journal of molecular sciences · 2023Review
- Repurposing Verapamil to Enhance Killing of T-ALL Cells by the mTOR Inhibitor Everolimus.Antioxidants (Basel, Switzerland) · 2023Article
- Simultaneous targeting of mitochondrial Kv1.3 and lysosomal acid sphingomyelinase amplifies killing of pancreatic ductal adenocarcinoma cells in vitro and in vivo.Journal of molecular medicine (Berlin, Germany) · 2023Article
- A Meta-Analysis Study to Infer Voltage-Gated KAntioxidants (Basel, Switzerland) · 2023Article
- Reduction of inflammation and mitochondrial degeneration in mutant SOD1 mice through inhibition of voltage-gated potassium channel Kv1.3.Frontiers in molecular neuroscience · 2023Article
- Article
- Design of New Potent and Selective Thiophene-Based KCancers · 2022Article
35 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Overcoming the resistance of tumours to chemotherapy, often due to downregulation of Bax and Bak, represents a significant clinical challenge. It is therefore important to identify novel apoptosis inducers that bypass Bax and Bak. Potassium channels are emerging as oncological targets and a crucial role of mitochondrial Kv1.3 in apoptosis has been demonstrated. Here we report for the first time that Psora-4, PAP-1 and clofazimine, three distinct membrane-permeant inhibitors of Kv1.3, induce death by directly targeting the mitochondrial channel in multiple human and mouse cancer cell lines. Importantly, these drugs activated the intrinsic apoptotic pathway also in the absence of Bax and Bak, a result in agreement with the current mechanistic model for mitochondrial Kv1.3 action. Genetic deficiency or short interfering RNA (siRNA)-mediated downregulation of Kv1.3 abrogated the effects of the drugs. Intraperitoneal injection of clofazimine reduced tumour size by 90% in an orthotopic melanoma B16F10 mouse model in vivo, while no adverse effects were observed in several healthy tissues. The study indicates that inhibition of mitochondrial Kv1.3 might be a novel therapeutic option for the induction of cancer cell death independent of Bax and Bak.
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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.