ArticleBritish journal of pharmacology2016
All-trans retinoic acid protects against doxorubicin-induced cardiotoxicity by activating the ERK2 signalling pathway.
Article in British journal of pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- A Systematic Review of the Potential Chemoprotective Effects of Resveratrol on Doxorubicin-Induced Cardiotoxicity: Focus on the Antioxidant, Antiapoptotic, and Anti-Inflammatory Activities.Oxidative medicine and cellular longevity · 2021Pooled it
- Retinoic acid in health and disease.Signal transduction and targeted therapy · 2026Review
- Paeoniflorin alleviates hypobaric hypoxia-triggered lung injury through targeting MEK2 to modulate ERK2-SGK1 signaling.Acta pharmaceutica Sinica. B · 2026Article
- Retinoic Acid and Calcitriol Protect Mouse Primordial Follicles from Cyclophosphamide Treatment-Induced Apoptosis.Antioxidants (Basel, Switzerland) · 2026Article
- Retinoic acid signaling and metabolism in heart failure.American journal of physiology. Heart and circulatory physiology · 2025Review
- At What Point Are Long-Term (>5 Years) Survivors of APL Safe? A Study from the SEER Database.Cancers · 2023Article
- Role of Nutrients and Foods in Attenuation of Cardiac Remodeling through Oxidative Stress Pathways.Antioxidants (Basel, Switzerland) · 2022Review
- All-Oncology letters · 2022Article
- Doxorubicin impacts chromatin binding of HMGB1, Histone H1 and retinoic acid receptor.Scientific reports · 2022Article
- All-trans retinoic acid (ATRA) regulates key genes in the RARG-TOP2B pathway and reduces anthracycline-induced cardiotoxicity.PloS one · 2022Article
- In Vitro and In Vivo Cardioprotective Effects of Curcumin against Doxorubicin-Induced Cardiotoxicity: A Systematic Review.Journal of oncology · 2022Review
- RARG variant predictive of doxorubicin-induced cardiotoxicity identifies a cardioprotective therapy.Cell stem cell · 2021Article
- Transcriptome-wide association study uncovers the role of essential genes in anthracycline-induced cardiotoxicity.NPJ genomic medicine · 2021Article
- Cardiac retinoic acid levels decline in heart failure.JCI insight · 2021Article
- Bioinformatic analysis of peripheral blood miRNA of breast cancer patients in relation with anthracycline cardiotoxicity.BMC cardiovascular disorders · 2020Article
- Study on Medication Rules of Traditional Chinese Medicine against Antineoplastic Drug-Induced Cardiotoxicity Based on Network Pharmacology and Data Mining.Evidence-based complementary and alternative medicine : eCAM · 2020Article
- 68Ga-Galmydar: A PET imaging tracer for noninvasive detection of Doxorubicin-induced cardiotoxicity.PloS one · 2019Article
- A Retinoic AcidThe Journal of pharmacology and experimental therapeutics · 2018Article
- Mitochondria-Targeting Small Molecules Effectively Prevent Cardiotoxicity Induced by Doxorubicin.Molecules (Basel, Switzerland) · 2018Review
- All-trans-retinoic acid ameliorates doxorubicin-induced cardiotoxicity: in vivo potential involvement of oxidative stress, inflammation, and apoptosis via caspase-3 and p53 down-expression.Naunyn-Schmiedeberg's archives of pharmacology · 2018Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeDoxorubicin is a powerful antineoplastic agent for treating a wide range of cancers. However, doxorubicin cardiotoxicity of the heart has largely limited its clinical use. All-trans retinoic acid (ATRA) plays an important role in many cardiac biological processes, but its protective effects on doxorubicin-induced cardiotoxicity remain unknown. Here, we studied the effect of ATRA on doxorubicin cardiotoxicity and the underlying mechanisms. EXPERIMENTAL APPROACHES: Cellular viability assays, Western blotting and mitochondrial respiration analyses were employed to evaluate the cellular response to ATRA in H9c2 cells and primary cardiomyocytes. Quantitative PCR and gene knockdown were performed to investigate the underlying molecular mechanisms of ATRA's effects on doxorubicin cardiotoxicity. KEY
resultsATRA significantly inhibited doxorubicin-induced apoptosis in H9c2 cells and primary cardiomyocytes. ATRA was more effective against doxorubicin cardiotoxicity than resveratrol and dexrazoxane. ATRA also suppressed reactive oxygen species generation and restored expression levels of mRNA and proteins in the phase II detoxifying enzyme system: nuclear factor-E2-related factor 2, manganese superoxide dismutase, haem oxygenase-1, and mitochondrial function (mitochondrial membrane integrity, mitochondrial DNA copy numbers and mitochondrial respiration capacity, biogenesis and dynamics). Both a ERK1/2 inhibitor (U0126) and ERK2 siRNA, but not ERK1 siRNA, abolished the protective effect of ATRA against doxorubicin-induced toxicity in H9c2 cells. Remarkably, ATRA did not compromise the anticancer efficacy of doxorubicin in gastric carcinoma cells. CONCLUSIONS AND IMPLICATIONS: ATRA protected cardiomyocytes against doxorubicin-induced toxicity, by activating the ERK2 pathway, without compromising its anticancer efficacy. Therefore, ATRA is a promising candidate as a cardioprotective agent against doxorubicin cardiotoxicity.
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