ArticleCirculation research2023
PDE10A Inactivation Prevents Doxorubicin-Induced Cardiotoxicity and Tumor Growth.
Article in Circulation research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Bibliometric and visual analysis of doxorubicin-induced cardiotoxicity.Frontiers in pharmacology · 2023Pooled it
- Temporal Mapping of CSVD-Related White Matter Lesions and Concurrent Neurovascular Dysfunction in Spontaneously Hypertensive Rats.CNS neuroscience & therapeutics · 2026Article
- Developing a Phosphodiesterase 10A Inhibitor as a Novel Therapeutic Agent for Triple-Negative Breast Cancer.Cells · 2026Article
- PD-1/PD-L1 inhibitor induces systemic inflammation and alters cardiac lipid metabolism in C57BL/6 J mice.Human cell · 2026Article
- CD74 deficiency protects against doxorubicin cardiotoxicity through RRM2-mediated regulation of ferroptosis.Acta pharmaceutica Sinica. B · 2026Article
- Filgotinib inhibits METTL3-mediated mNPJ precision oncology · 2026Article
- Lactylation at lysine 145 fosters KAT8-TIP60 complex formation to promote p53 acetylation at lysine 120 and its pro-apoptotic function.Nature communications · 2026Article
- Cyclic guanosine monophosphate-protein kinase G signaling attenuates aortic valve calcification through ULK1-mediated autophagy.Signal transduction and targeted therapy · 2026Article
- Herbacetin alleviates acute doxorubicin cardiotoxicity via regulating the ERK1/2-FOXO3a signaling pathway.Human cell · 2026Article
- Lithospermic Acid Improves Doxorubicin-Induced Cardiomyopathy Through Sirtuin-3-Mediated Deacetylation of p53.Phytotherapy research : PTR · 2026Article
- Prussian blue nanoparticles targeting multiple PANoptosome-mediated PANoptosis for myocardial ischemia-reperfusion injury therapy.Nature communications · 2026Article
- Review
- Sacubitril valsartan combined with bisoprolol reduces doxorubicin-induced cardiotoxicity in rats by attenuating oxidative stress.Experimental biology and medicine (Maywood, N.J.) · 2026Article
- BRD4770 protects against DOX-induced cardiotoxicity by inhibiting apoptosis and ferroptosis.Science advances · 2025Article
- Targeting RPLP2 Triggers DLBCL Ferroptosis by Decreasing FXN Expression.Biomedicines · 2025Article
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- Nanodomain cAMP signaling in cardiac pathophysiology: potential for developing targeted therapeutic interventions.Physiological reviews · 2025Review
- Crip2 affects vascular development by fine-tuning endothelial cell aggregation and proliferation.Cellular and molecular life sciences : CMLS · 2025Article
- Promoting proteostasis by cAMP/PKA and cGMP/PKG.Trends in molecular medicine · 2025Review
- Phosphodiesterase 10A Inhibitor Modulates Right Ventricular Outflow Tract Electrophysiological Activities and Calcium Homeostasis via the cGMP/PKG Pathway.Journal of cellular and molecular medicine · 2025Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundCyclic nucleotides play critical roles in cardiovascular biology and disease. PDE10A (phosphodiesterase 10A) is able to hydrolyze both cAMP and cGMP. PDE10A expression is induced in various human tumor cell lines, and PDE10A inhibition suppresses tumor cell growth. Chemotherapy drug such as doxorubicin (DOX) is widely used in chemotherapy. However, cardiotoxicity of DOX remains to be a serious clinical complication. In the current study, we aim to determine the role of PDE10A and the effect of PDE10A inhibition on cancer growth and cardiotoxicity induced by DOX.
methodsWe used global PDE10A knockout (KO) mice and PDE10A inhibitor TP-10 to block PDE10A function. DOX-induced cardiotoxicity was evaluated in C57Bl/6J mice and nude mice with implanted ovarian cancer xenografts. Isolated adult mouse cardiomyocytes and a human ovarian cancer cell line were used for in vitro functional and mechanistic studies.
resultsWe found that PDE10A deficiency or inhibition alleviated DOX-induced myocardial atrophy, apoptosis, and dysfunction in C57Bl/6J mice. RNA sequencing study revealed a number of PDE10A-regulated signaling pathways involved in DOX-induced cardiotoxicity. PDE10A inhibition increased the death, decreased the proliferation, and potentiated the effect of DOX on various human cancer cells. Importantly, in nude mice with implanted ovarian cancer xenografts, PDE10A inhibition attenuated tumor growth while protecting DOX-induced cardiotoxicity. In isolated cardiomyocytes, PDE10A contributed to DOX-induced cardiomyocyte death via increasing Top2β (topoisomerase 2β) expression, mitochondrial dysfunction, and DNA damage by antagonizing cGMP/PKG (protein kinase G) signaling. PDE10A contributed to cardiomyocyte atrophy via potentiating FoxO3 (forkhead box O3) signaling via both cAMP/PKA (protein kinase A)- and cGMP/PKG-dependent signaling.
conclusionsTaken together, our study elucidates a novel role for PDE10A in cardiotoxicity induced by DOX and cancer growth. Given that PDE10A has been already proven to be a safe drug target, PDE10A inhibition may represent a novel therapeutic strategy in cancer therapy, with effects preventing DOX-induced cardiotoxicity and simultaneously antagonizing cancer growth.
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