ArticleArchives of toxicology2020
GATA4-targeted compound exhibits cardioprotective actions against doxorubicin-induced toxicity in vitro and in vivo: establishment of a chronic cardiotoxicity model using human iPSC-derived cardiomyocytes.
Article in Archives of toxicology, 2020. 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, 30 citations in OpenAlex.
- Hypoplastic Left Heart Syndrome Cardiomyocytes Exhibit Intrinsic Stress Vulnerabilities and Augmented Stress Responses in vitro.Stem cell reviews and reports · 2026Article
- iPSC-derived cardiac organoids for drug cardiotoxicity evaluation and efficacy prediction in myocardial infarction and cardiac hypertrophy models.Stem cell research & therapy · 2026Article
- GATA4-targeted compounds induce apoptosis and diminish viability of hepatoblastoma cells.PloS one · 2026Article
- Update on preclinical models of cancer therapy-related cardiac dysfunction: Challenges and perspectives. A scientific statement of the Heart Failure Association (HFA) of the ESC, the ESC Council of Cardio-Oncology, and the ESC Working Group on Cellular Biology of the Heart.European journal of heart failure · 2025Review
- Understanding the Mechanisms of Chemotherapy-Related Cardiotoxicity Employing hiPSC-Derived Cardiomyocyte Models for Drug Screening and the Identification of Genetic and Epigenetic Variants.International journal of molecular sciences · 2025Review
- Cardiovascular Toxicity in Cancer Therapy: Protecting the Heart while Combating Cancer.Current cardiology reports · 2024Review
- Switching of hypertrophic signalling towards enhanced cardiomyocyte identity and maturity by a GATA4-targeted compound.Stem cell research & therapy · 2024Article
- Chronic Cardiotoxicity Assays Using Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes (hiPSC-CMs).International journal of molecular sciences · 2022Review
- Application of Human Induced Pluripotent Stem Cell Technology for Cardiovascular Regenerative Pharmacology.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Review
- Cinnamic Acid Derivatives as Cardioprotective Agents against Oxidative and Structural Damage Induced by Doxorubicin.International journal of molecular sciences · 2021Article
- GATA-targeted compounds modulate cardiac subtype cell differentiation in dual reporter stem cell line.Stem cell research & therapy · 2021Article
- Drug Development and the Use of Induced Pluripotent Stem Cell-Derived Cardiomyocytes for Disease Modeling and Drug Toxicity Screening.International journal of molecular sciences · 2020Review
- Pharmacological Protein Kinase C Modulators Reveal a Pro-hypertrophic Role for Novel Protein Kinase C Isoforms in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.Frontiers in pharmacology · 2020Article
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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
Doxorubicin is a widely used anticancer drug that causes dose-related cardiotoxicity. The exact mechanisms of doxorubicin toxicity are still unclear, partly because most in vitro studies have evaluated the effects of short-term high-dose doxorubicin treatments. Here, we developed an in vitro model of long-term low-dose administration of doxorubicin utilizing human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Moreover, given that current strategies for prevention and management of doxorubicin-induced cardiotoxicity fail to prevent cancer patients developing heart failure, we also investigated whether the GATA4-targeted compound 3i-1000 has cardioprotective potential against doxorubicin toxicity both in vitro and in vivo. The final doxorubicin concentration used in the chronic toxicity model in vitro was chosen based on cell viability data evaluation. Exposure to doxorubicin at the concentrations of 1-3 µM markedly reduced (60%) hiPSC-CM viability already within 48 h, while a 14-day treatment with 100 nM doxorubicin concentration induced only a modest 26% reduction in hiPCS-CM viability. Doxorubicin treatment also decreased DNA content in hiPSC-CMs. Interestingly, the compound 3i-1000 attenuated doxorubicin-induced increase in pro-B-type natriuretic peptide (proBNP) expression and caspase-3/7 activation in hiPSC-CMs. Moreover, treatment with 3i-1000 for 2 weeks (30 mg/kg/day, i.p.) inhibited doxorubicin cardiotoxicity by restoring left ventricular ejection fraction and fractional shortening in chronic in vivo rat model. In conclusion, the results demonstrate that long-term exposure of hiPSC-CMs can be utilized as an in vitro model of delayed doxorubicin-induced toxicity and provide in vitro and in vivo evidence that targeting GATA4 may be an effective strategy to counteract doxorubicin-induced cardiotoxicity.
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