ArticleThe Journal of biological chemistry2018
Inhibition of cyclin-dependent kinase 2 protects against doxorubicin-induced cardiomyocyte apoptosis and cardiomyopathy.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 40 citations in OpenAlex.
- Discovery of ZJC-11 as a Novel Selective CDK7 Inhibitor for Treating Triple-Negative Breast Cancer by Inducing Cell Senescence.Journal of medicinal chemistry · 2026Article
- Identification of RUNX1 as a Biomarker for Right Ventricular Remodeling in Pulmonary Arterial Hypertension Using WGCNA.Pulmonary circulation · 2026Article
- Network pharmacology-based therapeutic intervention of Mentha arvensis targeting cancer and doxorubicin-induced cardiotoxicity.Investigational new drugs · 2026Article
- Pediatric doxorubicin exposure induces persistent pathological changes in mice.Toxicology and applied pharmacology · 2025Article
- Inhibition of cyclin-dependent kinase 7 mitigates doxorubicin cardiotoxicity and enhances anticancer efficacy.Cardiovascular research · 2024Article
- New Insight Into Cardioprotection From Anthracyclines: Still Converging on the Mitochondria.JACC. CardioOncology · 2023Article
- Article
- Loss of Rbl2 (Retinoblastoma-Like 2) Exacerbates Myocardial Ischemia/Reperfusion Injury.Journal of the American Heart Association · 2022Article
- Therapeutic Targets for DOX-Induced Cardiomyopathy: Role of Apoptosis vs. Ferroptosis.International journal of molecular sciences · 2022Review
- Synthesis of Novel 2-Thiouracil-5-Sulfonamide Derivatives as Potent Inducers of Cell Cycle Arrest and CDK2A Inhibition Supported by Molecular Docking.International journal of molecular sciences · 2021Article
- Design of ferrocenylseleno-dopamine derivatives to optimize the Fenton-like reaction efficiency and antitumor efficacy.RSC advances · 2021Article
- Novel Mechanisms of Anthracycline-Induced Cardiovascular Toxicity: A Focus on Thrombosis, Cardiac Atrophy, and Programmed Cell Death.Frontiers in cardiovascular medicine · 2021Review
- Synthesis, crystal structure and antiproliferative mechanisms of gallium(iii) complexes with benzoylpyridine thiosemicarbazones.RSC advances · 2020Article
- Doxorubicin induces cardiomyocyte apoptosis and atrophy through cyclin-dependent kinase 2-mediated activation of forkhead box O1.The Journal of biological chemistry · 2020Article
- PRKAR1A deficiency impedes hypertrophy and reduces heart size.Physiological reports · 2020Article
- Enhanced Antitumor Efficacy of Macrophage-Mediated Egg Yolk Lipid-Derived Delivery System Against Breast Cancer.International journal of nanomedicine · 2020Article
- Unique Phenotypes of Heart Resident Type 2 Innate Lymphoid Cells.Frontiers in immunology · 2020Article
- Cell Cycle Proteins as Key Regulators of Postmitotic Cell Death.The Yale journal of biology and medicine · 2019Review
- Remote Ischemic Pre-Conditioning Attenuates Adverse Cardiac Remodeling and Mortality Following Doxorubicin Administration in Mice.JACC. CardioOncology · 2019Article
- Integrative Bioinformatics Approaches to Map Potential Novel Genes and Pathways Involved in Ovarian Cancer.Frontiers in bioengineering and biotechnology · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
With the rapid increase in cancer survival because of improved diagnosis and therapy in the past decades, cancer treatment-related cardiotoxicity is becoming an urgent healthcare concern. The anthracycline doxorubicin (DOX), one of the most effective chemotherapeutic agents to date, causes cardiomyopathy by inducing cardiomyocyte apoptosis. We demonstrated previously that overexpression of the cyclin-dependent kinase (CDK) inhibitor p21 promotes resistance against DOX-induced cardiomyocyte apoptosis. Here we show that DOX exposure provokes cardiac CDK2 activation and cardiomyocyte cell cycle S phase reentry, resulting in enhanced cellular sensitivity to DOX. Genetic or pharmacological inhibition of CDK2 markedly suppressed DOX-induced cardiomyocyte apoptosis. Conversely, CDK2 overexpression augmented DOX-induced apoptosis. We also found that DOX-induced CDK2 activation in the mouse heart is associated with up-regulation of the pro-apoptotic BCL2 family member BCL2-like 11 (Bim), a BH3-only protein essential for triggering Bax/Bak-dependent mitochondrial outer membrane permeabilization. Further experiments revealed that DOX induces cardiomyocyte apoptosis through CDK2-dependent expression of Bim. Inhibition of CDK2 with roscovitine robustly repressed DOX-induced mitochondrial depolarization. In a cardiotoxicity model of chronic DOX exposure (5 mg/kg weekly for 4 weeks), roscovitine administration significantly attenuated DOX-induced contractile dysfunction and ventricular remodeling. These findings identify CDK2 as a key determinant of DOX-induced cardiotoxicity. CDK2 activation is necessary for DOX-induced Bim expression and mitochondrial damage. Our results suggest that pharmacological inhibition of CDK2 may be a cardioprotective strategy for preventing anthracycline-induced heart damage.
Indexed as
Identifiers
What OpenQuestion holds
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.