ArticleOncotarget2016
A small molecule inhibitor of PAI-1 protects against doxorubicin-induced cellular senescence.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
What it found
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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
58 citing papers in PubMed, 91 citations in OpenAlex.
- SERPINE1 (PAI-1) Regulation in Mechanotransduction-Associated Cellular Senescence.Journal of cellular biochemistry · 2026Review
- Review
- SWATH-MS for discovery of early biomarkers of drug-induced cardiotoxicity using an animal doxorubicin model.Cardio-oncology (London, England) · 2026Article
- Review
- PAI-1 is a common driver of aging and diverse diseases.Biomedical journal · 2026Review
- Inhibition of PAI-1 shifts cardiomyocyte fate from senescence toward apoptosis and mitigates doxorubicin-induced cardiotoxicity.Geromedicine · 2026Article
- Plasma Plasminogen Activator Inhibitor-1 as a Biomarker for Disease Activity and Pharmaco-Response Prediction in Pediatric Epilepsy: A Prospective Cohort Study.Neuropsychiatric disease and treatment · 2026Article
- PAI-1: A Key Signal at the Crossroads of Stem Cell Differentiation and Senescence.International journal of molecular sciences · 2025Review
- INHIBITING THE INHIBITOR: WOULD TARGETING PAI-1 RESULT IN A LOW-DOSE, WELL-TOLERATED TREATMENT OF EMPYEMA?Biomedical sciences instrumentation · 2025Article
- Molecular Regulation of SASP in Cellular Senescence: Therapeutic Implications and Translational Challenges.Cells · 2025Review
- Persisting blood-brain barrier disruption following cisplatin treatment in a mouse model of chemotherapy-associated cognitive impairment.GeroScience · 2025Article
- Klotho protects INS-1 pancreatic β-cells from senescence and enhances mitochondrial function.Frontiers in aging · 2025Article
- Role of plasminogen activator inhibitor-1 (PAI-1) in age-related cardiovascular pathophysiology.The journal of cardiovascular aging · 2025Article
- A signaling pathway map of plasminogen activator inhibitor-1 (PAI-1/SERPINE-1): a review of an innovative frontier in molecular aging and cellular senescence.Cell communication and signaling : CCS · 2024Review
- Recent Advances in the Mechanisms of Cell Death and Dysfunction in Doxorubicin Cardiotoxicity.Reviews in cardiovascular medicine · 2023Review
- Article
- CO-Induced TTP Activation Alleviates Cellular Senescence and Age-Dependent Hepatic SteatosisAging and disease · 2023Article
- Therapeutic opportunities for senolysis in cardiovascular disease.The FEBS journal · 2023Review
- Mechanisms and consequences of endothelial cell senescence.Nature reviews. Cardiology · 2023Review
- Mitochondrial Dynamin-Related Protein Drp1: a New Player in Cardio-oncology.Current oncology reports · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Doxorubicin, an anthracycline antibiotic, is a commonly used anticancer drug. In spite of its widespread usage, its therapeutic effect is limited by its cardiotoxicity. On the cellular level, Doxorubicin-induced cardiotoxicity manifests as stress induced premature senescence. Previously, we demonstrated that plasminogen activator inhibitor-1 (PAI-1), a potent inhibitor of serine proteases, is an important biomarker and regulator of cellular senescence and aging. Here, we tested the hypothesis that pharmacological inhibition of cellular PAI-1 protects against stress- and aging-induced cellular senescence and delineated the molecular basis of protective action of PAI-1 inhibition. Results show that TM5441, a potent small molecule inhibitor of PAI-1, effectively prevents Doxorubicin-induced senescence in cardiomyocytes, fibroblasts and endothelial cells. TM5441 exerts its inhibitory effect on Doxorubicin-induced cellular senescence by decreasing reactive oxygen species generation, induction of antioxidants like catalase and suppression of stress-induced senescence cadre p53, p21, p16, PAI-1 and IGFBP3. Importantly, TM5441 also reduces replicative senescence of fibroblasts. Together these results for the first time demonstrate the efficacy of PAI-1 inhibitor in prevention of Doxorubicin-induced and replicative senescence in normal cells. Thus PAI-1 inhibitor may form an important adjuvant component of chemotherapy regimens, limiting not only Doxorubicin-induced cardiac senescence but also ameliorating the prothrombotic profile.
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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.