ArticlePloS one2013
Catalytic inhibitors of topoisomerase II differently modulate the toxicity of anthracyclines in cardiac and cancer cells.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 70 citations in OpenAlex.
- Mechanisms of Doxorubicin-Induced Cardiac Senescence and Potential Therapeutic Strategies.Biomolecules · 2026Review
- Novel Mechanism of and Therapeutic Approach for Anthracycline-Induced Cardiotoxicity.Cancer research communications · 2026Article
- Daunorubicin and its hydroxy metabolite in cardiomyocytes: insights into cellular kinetics, toxicity, DNA damage, and dexrazoxane-induced cardioprotection.Archives of toxicology · 2025Article
- SiRNA-mediated knockdown of TOP2B protects hiPSC-derived cardiomyocytes from doxorubicin-induced toxicity.Life sciences · 2025Article
- Tetrahedral Framework Nucleic Acids Inhibit Oxidative Stress and Cardiomyocyte Apoptosis in Doxorubicin-Induced Cardiotoxicity.International journal of nanomedicine · 2025Article
- Dexrazoxane prevents vascular toxicity in doxorubicin-treated mice.Cardio-oncology (London, England) · 2024Article
- A review of the pathophysiological mechanisms of doxorubicin-induced cardiotoxicity and aging.npj aging · 2024Review
- An update of the molecular mechanisms underlying anthracycline induced cardiotoxicity.Frontiers in pharmacology · 2024Review
- Article
- Global Longitudinal Strain Monitoring to Guide Cardioprotective Medications During Anthracycline Treatment.Current oncology reports · 2022Review
- A Microfluidic Multisize Spheroid Array for Multiparametric Screening of Anticancer Drugs and Blood-Brain Barrier Transport Properties.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Mitoxantrone impairs proteasome activity and prompts early energetic and proteomic changes in HL-1 cardiomyocytes at clinically relevant concentrations.Archives of toxicology · 2020Article
- Article
- The Role of Oxidative Stress in Physiopathology and Pharmacological Treatment with Pro- and Antioxidant Properties in Chronic Diseases.Oxidative medicine and cellular longevity · 2020Review
- Detection of subclinical cardiotoxicity in sarcoma patients receiving continuous doxorubicin infusion or pre-treatment with dexrazoxane before bolus doxorubicin.Cardio-oncology (London, England) · 2020Article
- UHPLC-MS/MS method for analysis of sobuzoxane, its active form ICRF-154 and metabolite EDTA-diamide and its application to bioactivation study.Scientific reports · 2019Article
- Pediatric Anthracycline-Induced Cardiotoxicity: Mechanisms, Pharmacogenomics, and Pluripotent Stem-Cell Modeling.Clinical pharmacology and therapeutics · 2019Review
- Clinically Applicable Inhibitors Impacting Genome Stability.Molecules (Basel, Switzerland) · 2018Review
- Topoisomerases as anticancer targets.The Biochemical journal · 2018Review
- The cardioprotective effect of dexrazoxane (Cardioxane) is consistent with sequestration of poly(ADP-ribose) by self-assembly and not depletion of topoisomerase 2B.Ecancermedicalscience · 2018Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Anthracyclines (such as doxorubicin or daunorubicin) are among the most effective anticancer drugs, but their usefulness is hampered by the risk of irreversible cardiotoxicity. Dexrazoxane (ICRF-187) is the only clinically approved cardioprotective agent against anthracycline cardiotoxicity. Its activity has traditionally been attributed to the iron-chelating effects of its metabolite with subsequent protection from oxidative stress. However, dexrazoxane is also a catalytic inhibitor of topoisomerase II (TOP2). Therefore, we examined whether dexrazoxane and two other TOP2 catalytic inhibitors, namely sobuzoxane (MST-16) and merbarone, protect cardiomyocytes from anthracycline toxicity and assessed their effects on anthracycline antineoplastic efficacy. Dexrazoxane and two other TOP2 inhibitors protected isolated neonatal rat cardiomyocytes against toxicity induced by both doxorubicin and daunorubicin. However, none of the TOP2 inhibitors significantly protected cardiomyocytes in a model of hydrogen peroxide-induced oxidative injury. In contrast, the catalytic inhibitors did not compromise the antiproliferative effects of the anthracyclines in the HL-60 leukemic cell line; instead, synergistic interactions were mostly observed. Additionally, anthracycline-induced caspase activation was differentially modulated by the TOP2 inhibitors in cardiac and cancer cells. Whereas dexrazoxane was upon hydrolysis able to significantly chelate intracellular labile iron ions, no such effect was noted for either sobuzoxane or merbarone. In conclusion, our data indicate that dexrazoxane may protect cardiomyocytes via its catalytic TOP2 inhibitory activity rather than iron-chelation activity. The differential expression and/or regulation of TOP2 isoforms in cardiac and cancer cells by catalytic inhibitors may be responsible for the selective modulation of anthracycline action observed.
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