ArticleAging2023
Doxorubicin induced ROS-dependent HIF1α activation mediates blockage of IGF1R survival signaling by IGFBP3 promotes cardiac apoptosis.
Article in Aging, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 18 citations in OpenAlex.
- Ru3: a novel ruthenium-based compound overcomes cisplatin resistance in non-small cell lung cancer via the E2F2-IGFBP3-GPX4 pathway.Apoptosis : an international journal on programmed cell death · 2026Article
- IGFBP3 and cisplatin synergistically suppress HeLa cell proliferation and migration through NRF2 inhibition.Research in pharmaceutical sciences · 2026Article
- Amifostine Attenuates Doxorubicin-Induced Subacute Hepatic and Renal Toxicity in Rats.International journal of molecular sciences · 2026Article
- Impact of CaInternational journal of molecular sciences · 2026Review
- Identification of TGF-β1 as a key regulator in DOX-induced cardiotoxicity.Journal of cardiothoracic surgery · 2026Article
- Synergistic cytotoxicity of recombinant IGFBP-3 and cisplatin in HPV18-positive HeLa cellsResearch in pharmaceutical sciences · 2026Article
- PDZRN4 suppresses lung adenocarcinoma progression via inhibiting ubiquitin-mediated HIF-1A degradation.Oncogene · 2026Article
- Aryl Hydrocarbon Receptor (AhR) and Vascular Endothelial Growth Factor (VEGF) Crosstalk in Doxorubicin Nephrotoxicity: Mechanisms and Therapeutic Perspectives.Current issues in molecular biology · 2026Article
- Soluble neprilysin is associated with myocardial damage and systolic dysfunction in an animal model of doxorubicin-induced cardiotoxicity.Cardio-oncology (London, England) · 2026Article
- Neuraminidase 1 Exacerbated Glycolytic Dysregulation and Cardiotoxicity by Destabilizing SIRT1 through Interactions with NRF2 and HIF1α.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Controllable nickel ions release from deferoxamine mesylate-triggered nickel-iron layered double hydroxide for eliciting apoptotic cell death in prostate cancer.Journal of nanobiotechnology · 2025Article
- Potential Mechanism by which Eriodictyol Protects against Doxorubicininduced Cardiotoxicity based on Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation.Current computer-aided drug design · 2025Article
- MiR-668-5p targets ZNRF3, an E3 ubiquitin ligase to enhance osteoblast function and alleviate senescence in doxorubicin-induced age-related bone loss.Frontiers in endocrinology · 2025Article
- Coordinated regulation of IGF1R by HIF1α and HIF2α enhances chemoresistance in glioblastoma.Frontiers in pharmacology · 2025Article
- Single molecule tracking based drug screening.Nature communications · 2024Article
- Oxidative Stress-Responsive Apoptosis Inducing Protein (ORAIP) Plays a Critical Role in Dextran Sulfate Sodium-Induced Murine Model of Ulcerative Colitis.Medicina (Kaunas, Lithuania) · 2024Article
- Doxorubicin Attenuates Free Fatty Acid-Induced Lipid Accumulation via Stimulation of p53 in HepG2 Cells.Biomolecules & therapeutics · 2024Article
- Identification of cellular senescence-related genes and immune cell infiltration characteristics in intervertebral disc degeneration.Frontiers in immunology · 2024Article
- Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Doxorubicin (Dox) causes the generation of intracellular reactive oxygen species (ROS) and inactivates insulin-like growth factor 1 (IGF1) signaling, leading to cardiomyocyte apoptosis. IGF-binding protein 3 (IGFBP3) is the most abundant circulating IGF1 carrier protein with high affinity, which has been reported to mediate ROS-induced apoptosis. Hypoxia-inducible factor 1α (HIF1A), an upstream protein of IGFBP3 is regulated by prolyl hydroxylase domain (PHD) through hydroxylation. In this study, we investigated the role of IGFBP3, HIF1A, and PHD in Dox-induced cardiac apoptosis.Cells challenged with 1 μM Dox for 24 h increased ROS generation, augmented intracellular and secreted IGFBP3 levels, and reduced IGF1 signaling. Further, we showed that Dox enhanced the extracellular association of IGF1 with IGFBP3. Moreover, echocardiography parameters, especially ejection fraction (EF) and fractional shortening (FS) were significantly reduced in ventricle tissue of Dox challenged rats. Notably, siRNA approach against IGFBP3 or an anti-IGFBP3 antibody rescued Dox-induced cardiac apoptosis, mitochondrial ROS, and the decrease in the IGF1 signaling activity. Furthermore, silencing HIF1A either using siRNA or inhibitor downregulated intracellular IGFBP3, rescued apoptosis, mitochondrial generation, and reduction in IGF1 signaling. Finally, western blot data revealed that ROS scavenger reversed Dox-induced cardiac apoptosis, increased levels of HIF1A and secreted IGFBP3, and decreased IGF1 survival signaling and PHD expression.These findings suggest that Dox-induced ROS generation suppressed PHD, which might stabilize nuclear HIF1A protein, leading to increased IGFBP3 expression and secretion. This in turn results in enhanced extracellular association of the latter with IGF1 and blocks IGF1 pro-survival signaling and may result in inducing cardiac apoptosis.
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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.