ArticlePloS one2014
Metformin protects cardiomyocyte from doxorubicin induced cytotoxicity through an AMP-activated protein kinase dependent signaling pathway: an in vitro study.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 132 citations in OpenAlex.
- Effects of metformin and donepezil on the prevention of doxorubicin-induced cardiotoxicity in breast cancer: a randomized controlled trial.Scientific reports · 2023Trial
- Effects of high-intensity aerobic exercise during multiple cycles of doxorubicin treatment on cardiac catabolism.Physical activity and nutrition · 2026Article
- Network pharmacology-based therapeutic intervention of Mentha arvensis targeting cancer and doxorubicin-induced cardiotoxicity.Investigational new drugs · 2026Article
- Role of solute carrier transporters in the biodistribution and toxicity of chemotherapeutic drugs.Pharmacological reviews · 2026Review
- Evaluation of metformin's effect on 5-fluorouracil-induced cardiotoxicity through cellular protection.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2026Article
- Review
- Repurposing metformin for cardioprotection: mechanisms and therapeutic potential across cardiovascular pathologies.Frontiers in pharmacology · 2026Review
- Alteration of cardiac energetics and mitochondrial function in doxorubicin‑induced cardiotoxicity: Molecular mechanism and prospective implications (Review).International journal of molecular medicine · 2025Review
- Streptozotocin-induced hyperglycemia unmasks cardiotoxicity induced by doxorubicin.Scientific reports · 2025Article
- Doxorubicin or Epirubicin Versus Liposomal Doxorubicin Therapy-Differences in Cardiotoxicity.Cardiovascular toxicology · 2025Review
- Unveiling the Protective Role of Metformin against Chemotherapy-induced Cardiotoxicity: A Comprehensive Scoping Review on Non-clinical Studies.Current medicinal chemistry · 2025Article
- Memantine, an NMDA Receptor Antagonist, Attenuates Doxorubicin-Induced Cardiac Oxidative Stress and Inflammation in Mouse 4T1 Breast Cancer Model.Breast cancer : basic and clinical research · 2025Article
- Rivaroxaban Ameliorates Sunitinib-Induced Injury of Cardiomyocytes via Repressing MAPK Signaling Pathway.Cardiovascular therapeutics · 2025Article
- Anti-Diabetic Therapies and Cancer: From Bench to Bedside.Biomolecules · 2024Review
- HAPLN1 knockdown inhibits heart failure development via activating the PKA signaling pathway.BMC cardiovascular disorders · 2024Article
- Article
- Dehydroevodiamine Alleviates Doxorubicin-Induced Cardiomyocyte Injury by Regulating Neuregulin-1/ErbB Signaling.Cardiovascular therapeutics · 2024Article
- [Metformin mitigates doxorubicin-induced cardiotoxicityNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2023Article
- Nrf2: a dark horse in doxorubicin-induced cardiotoxicity.Cell death discovery · 2023Review
- The development and benefits of metformin in various diseases.Frontiers of medicine · 2023Review
11 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Doxorubicin (Dox) is one of the most widely used antitumor drugs, but its cumulative cardiotoxicity have been major concerns in cancer therapeutic practice for decades. Recent studies established that metformin (Met), an oral anti-diabetic drug, provides protective effects in Dox-induced cardiotoxicity. Met has been shown to increase fatty acid oxidation, an effect mediated by AMP activated protein kinase (AMPK). Here we delineate the intracellular signaling factors involved in Met mediated protection against Dox-induced cardiotoxicity in the H9c2 cardiomyoblast cell line. Treatment with low dose Met (0.1 mM) increased cell viabilities and Ki-67 expressions while decreasing LDH leakages, ROS generations and [Ca2+]i. The protective effect was reversed by a co-treatment with compound-C, an AMPK specific inhibitor, or by an over expression of a dominant-negative AMPKα cDNA. Inhibition of PKA with H89 or a suppression of Src kinase by a small hairpin siRNA also abrogated the protective effect of the low dose Met. Whereas, with a higher dose of Met (1.0 mM), the protective effects were abolished regardless of the enhanced AMPK, PKA/CREB1 and Src kinase activity. In high dose Met treated cells, expression of platelet-derived growth factor receptor (PDGFR) was significantly suppressed. Furthermore, the protective effect of low dose Met was totally reversed by co-treatment with AG1296, a PDGFR specific antagonist. These data provide in vitro evidence supporting a signaling cascade by which low dose Met exerts protective effects against Dox via sequential involvement of AMPK, PKA/CREB1, Src and PDGFR. Whereas high dose Met reverses the effect by suppressing PDGFR expression.
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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.