ArticlePloS one2018
Electrophysiological mechanisms of vandetanib-induced cardiotoxicity: Comparison of action potentials in rabbit Purkinje fibers and pluripotent stem cell-derived cardiomyocytes.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- Drug Proarrhythmic Evaluation in a High Throughput Cardiac New Approach Methodology.bioRxiv : the preprint server for biology · 2026Article
- A thioridazine-derived molecule exhibits potential anti-inflammatory activity through IKK inhibition.Inflammopharmacology · 2025Article
- Immuno-inflammatory mechanisms in cardio-oncology: new hopes for immunotargeted therapies.Frontiers in oncology · 2025Review
- Quantitative Structure-Activity Relationship Models to Predict Cardiac Adverse Effects.Chemical research in toxicology · 2024Article
- Atrial fibrillation in cancer, anticancer therapies, and underlying mechanisms.Journal of molecular and cellular cardiology · 2024Review
- Gellan gum-gelatin based cardiac models support formation of cellular networks and functional cardiomyocytes.Cytotechnology · 2024Article
- Vascularised cardiac spheroids-on-a-chip for testing the toxicity of therapeutics.Scientific reports · 2024Article
- Investigating the effect of vandetanib and celecoxib combination on angiogenesis.Journal of Taibah University Medical Sciences · 2023Article
- Concept of Hybrid Drugs and Recent Advancements in Anticancer Hybrids.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Functional human cell-based vascularised cardiac tissue model for biomedical research and testing.Scientific reports · 2022Article
- Article
- Cardiovascular Risks with Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors and Monoclonal Antibody Therapy.Current oncology reports · 2022Review
- Antiviral and anti-inflammatory drugs to combat COVID-19: Effects on cardiac ion channels and risk of ventricular arrhythmias.BioImpacts : BI · 2022Review
- The resting membrane potential of hSC-CM in a syncytium is more hyperpolarised than that of isolated cells.Channels (Austin, Tex.) · 2021Article
- Ginsenoside Rg3 Alleviates Antithyroid Cancer Drug Vandetanib-Induced QT Interval Prolongation.Oxidative medicine and cellular longevity · 2021Article
- Cardiac hERG KHandbook of experimental pharmacology · 2021Article
- Use of hiPSC to explicate genomic predisposition to anthracycline-induced cardiotoxicity.Pharmacogenomics · 2021Review
- Onco-Cardiology: Consensus Paper of the German Cardiac Society, the German Society for Pediatric Cardiology and Congenital Heart Defects and the German Society for Hematology and Medical Oncology.Clinical research in cardiology : official journal of the German Cardiac Society · 2020Review
- Human In Vitro Models for Assessing the Genomic Basis of Chemotherapy-Induced Cardiovascular Toxicity.Journal of cardiovascular translational research · 2020Review
- hiPSCs in cardio-oncology: deciphering the genomics.Cardiovascular research · 2019Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vandetanib, a multi-kinase inhibitor used for the treatment of various cancers, has been reported to induce several adverse cardiac effects. However, the underlying mechanisms of vandetanib-induced cardiotoxicity are unclear. This study aimed to investigate the mechanism of vandetanib-induced cardiotoxicity using intracellular electrophysiological recordings on human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), rabbit Purkinje fibers, and HEK293 cells transiently expressing human ether-a-go-go-related gene (hERG; the rapidly activating delayed rectifier K+ channel, IKr), KCNQ1/KCNE1 (the slowly activating delayed rectifier K+ current, IKs), KCNJ2 (the inwardly rectifying K+ current, IK1) or SCN5A (the inward Na+ current, INa). Purkinje fiber assays and ion channel studies showed that vandetanib at concentrations of 1 and 3 μM inhibited the hERG currents and prolonged the action potential duration. Alanine scanning and in silico hERG docking studies demonstrated that Y652 and F656 in the hERG S6 domain play critical roles in vandetanib binding. In hiPSC-CMs, vandetanib markedly reduced the maximum rate of depolarization during the AP upstroke. Ion channel studies revealed that hiPSC-CMs were more sensitive to inhibition of the INa by vandetanib than in a heterogeneously expressed HEK293 cell model, consistent with the changes in the AP parameters of hiPSC-CMs. The subclasses of Class I antiarrhythmic drugs inhibited INa currents in a dose-dependent manner in hiPSC-CMs and SCN5A-encoded HEK293 cells. The inhibitory potency of vandetanib for INa was much higher in hiPSC-CMs (IC50: 2.72 μM) than in HEK293 cells (IC50: 36.63 μM). These data suggest that AP and INa assays using hiPSC-CMs are useful electrophysiological models for prediction of drug-induced cardiotoxicity.
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