ArticleThe Journal of biological chemistry2020
Doxorubicin induces cardiomyocyte apoptosis and atrophy through cyclin-dependent kinase 2-mediated activation of forkhead box O1.
Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 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
51 citing papers in PubMed, 82 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
- Anti-PD-1 immune checkpoint inhibitor-induced cardiotoxicity is associated with dysfunctional metabolism, muscle wasting and autophagy.Scientific reports · 2026Article
- Psychosocial stress exacerbates doxorubicin-induced cardiotoxicity in adult C57BL/6N mice.Research square · 2026Article
- Integrative Network Pharmacology and Molecular Docking-Based Validation of Berberine as a Therapeutic Agent in Arsenic-Induced Cardiotoxicity.Cardiovascular toxicology · 2026Article
- Article
- Substrain-Dependent Differences in Doxorubicin-Induced Cardiotoxicity in Adult C57BL/6 Mice.Cardiovascular toxicology · 2025Article
- FOXO1 phosphorylation as a context-dependent molecular switch in cancer: from mechanisms to precision therapy.World journal of surgical oncology · 2025Review
- Pediatric doxorubicin exposure induces persistent pathological changes in mice.Toxicology and applied pharmacology · 2025Article
- High intensity interval training and dalteparin attenuate doxorubicin induced cardiac damage and FoxO4 protein level in rats.Scientific reports · 2025Article
- Review
- PCSK9 Inhibitor Inclisiran Attenuates Cardiotoxicity Induced by Sequential Anthracycline and Trastuzumab Exposure via NLRP3 and MyD88 Pathway Inhibition.International journal of molecular sciences · 2025Article
- Advances in Targeted Autophagy Modulation Strategies to Treat Cancer and Associated Treatment-Induced Cardiotoxicity.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Maturation of human induced pluripotent stem cell-derived cardiomyocytes promoted by Brachyury priming.Scientific reports · 2025Article
- Metformin Alleviates Doxorubicin-Induced Cardiotoxicity via Preserving Mitochondrial Dynamics Balance and Calcium Homeostasis.Applied biochemistry and biotechnology · 2025Article
- Cardiomyopathies and a brief insight into DOX-induced cardiomyopathy.The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology · 2025Review
- Review
- Preventive effect of imperatorin against doxorubicin-induced cardiotoxicity through suppression of NLRP3 inflammasome activation.Journal of natural medicines · 2025Article
- Cardiomyocyte GSDME Drives Doxorubicin-Induced Cardiotoxicity by Targeting the CCL2-CCR2 Axis.International journal of biological sciences · 2025Article
- Unveiling the Complexities: Exploring Mechanisms of Anthracyclineinduced Cardiotoxicity.Current cardiology reviews · 2025Review
- Differential cardiac impacts of hematological malignancies and solid tumors: a histopathological and biomarker study.Cardio-oncology (London, England) · 2024Article
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 3 institutions in 1 country.
Funding
Abstract
Recent clinical investigations indicate that anthracycline-based chemotherapies induce early decline in heart mass in cancer patients. Heart mass decline may be caused by a decrease in cardiac cell number because of increased cell death or by a reduction in cell size because of atrophy. We previously reported that an anthracycline, doxorubicin (DOX), induces apoptotic death of cardiomyocytes by activating cyclin-dependent kinase 2 (CDK2). However, the signaling pathway downstream of CDK2 remains to be characterized, and it is also unclear whether the same pathway mediates cardiac atrophy. Here we demonstrate that DOX exposure induces CDK2-dependent phosphorylation of the transcription factor forkhead box O1 (FOXO1) at Ser-249, leading to transcription of its proapoptotic target gene, Bcl-2-interacting mediator of cell death (Bim). In cultured cardiomyocytes, treatment with the FOXO1 inhibitor AS1842856 or transfection with FOXO1-specific siRNAs protected against DOX-induced apoptosis and mitochondrial damage. Oral administration of AS1842856 in mice abrogated apoptosis and prevented DOX-induced cardiac dysfunction. Intriguingly, pharmacological FOXO1 inhibition also attenuated DOX-induced cardiac atrophy, likely because of repression of muscle RING finger 1 (MuRF1), a proatrophic FOXO1 target gene. In conclusion, DOX exposure induces CDK2-dependent FOXO1 activation, resulting in cardiomyocyte apoptosis and atrophy. Our results identify FOXO1 as a promising drug target for managing DOX-induced cardiotoxicity. We propose that FOXO1 inhibitors may have potential as cardioprotective therapeutic agents during cancer chemotherapy.
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.