ArticleInvestigational new drugs2012
The histone deacetylase inhibitor butyroyloxymethyl diethylphosphate (AN-7) protects normal cells against toxicity of anticancer agents while augmenting their anticancer activity.
Article in Investigational new drugs, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 39 citations in OpenAlex.
- Exploring the basis of Traditional Chinese Medicine in treating cardiovascular disease: insights into the microbiota-gut-heart axis.Chinese medicine · 2026Review
- Role of gut microbiota in doxorubicin-induced cardiotoxicity: from pathogenesis to related interventions.Journal of translational medicine · 2024Review
- An update of the molecular mechanisms underlying anthracycline induced cardiotoxicity.Frontiers in pharmacology · 2024Review
- p53 at the Crossroads between Doxorubicin-Induced Cardiotoxicity and Resistance: A Nutritional Balancing Act.Nutrients · 2023Review
- Metabolic Aspects of Anthracycline Cardiotoxicity.Current treatment options in oncology · 2021Review
- Review on the Role of Epigenetic Modifications in Doxorubicin-Induced Cardiotoxicity.Frontiers in cardiovascular medicine · 2020Review
- Possible Susceptibility Genes for Intervention against Chemotherapy-Induced Cardiotoxicity.Oxidative medicine and cellular longevity · 2020Review
- The Histone Deacetylase Inhibitor AN7, Attenuates Choroidal Neovascularization in a Mouse Model.International journal of molecular sciences · 2019Article
- AN-7, a butyric acid prodrug, sensitizes cutaneous T-cell lymphoma cell lines to doxorubicin via inhibition of DNA double strand breaks repair.Investigational new drugs · 2018Article
- Regulation of Cellular Redox Signaling by Matricellular Proteins in Vascular Biology, Immunology, and Cancer.Antioxidants & redox signaling · 2017Article
- Effects of histone deacetylase inhibitory prodrugs on epigenetic changes and DNA damage response in tumor and heart of glioblastoma xenograft.Investigational new drugs · 2017Article
- Article
- The predominant protective effect of tianeptine over other antidepressants in models of neuronal apoptosis: the effect blocked by inhibitors of MAPK/ERK1/2 and PI3-K/Akt pathways.Neurotoxicity research · 2014Article
- Deregulated chromatin remodeling in the pathobiology of brain tumors.Neuromolecular medicine · 2013Review
- Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The histone deacetylase inhibitor (HDACI) butyroyloxymethyl diethylphosphate (AN-7) has been shown to synergize doxorubicin (Dox) anticancer activity while attenuating its cardiotoxicity. In this study we further explored the selectivity of AN-7's action in several cancer and normal cells treated with anticancer agents. The cells studied were murine mammary 4T1, human breast T47D and glioblastoma U251 cancer cell lines, neonatal rat cardiomyocytes, cardiofibroblasts and astrocytes, and immortalized cardiomyocyte H9C2 cells. Cell death, ROS production and changes in protein expression were measured and in vivo effects were evaluated in Balb-c mice. AN-7 synergized Dox and anti-HER2 cytotoxicity against mammary carcinoma cells with combination indices of 0.74 and 0.79, respectively, while it protected cardiomyocytes against their toxicity. Additionally AN-7 protected astrocytes from Dox-cytoxicity. Cell-type specific changes in the expression of proteins controlling survival, angiogenesis and inflammation by AN-7 or AN-7+Dox were observed. In mice, the protective effect of AN-7 against Dox cardiotoxicity was associated with a reduction in inflammatory factors. In summary, AN-7 augmented the anticancer activity of Dox and anti-HER2 and attenuated their toxicity against normal cells. AN-7 modulation of c-Myc, thrombospondin-1, lo-FGF-2 and other proteins were cell type specific. The effects of AN-7, Dox and their combination were preserved in vivo indicating the potential benefit of combining AN-7 and Dox for clinical use.
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