ArticleCell death & disease2015
Selective inhibition of HDAC8 decreases neuroblastoma growth in vitro and in vivo and enhances retinoic acid-mediated differentiation.
Article in Cell death & disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
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Who cites it
96 citing papers in PubMed, 175 citations in OpenAlex.
- Phase I/II intra-patient dose escalation study of vorinostat in children with relapsed solid tumor, lymphoma, or leukemia.Clinical epigenetics · 2019Trial
- The histone deacetylase family in health and disease.Signal transduction and targeted therapy · 2026Review
- Histone Deacetylase Meets Protein Degradation: Accelerating Anticancer Drug Discovery.Medicinal research reviews · 2026Review
- CXorf67 in malignancies: Deciphering epigenetic landscapes and clinical implications for precision oncology.Genes & diseases · 2026Review
- Electrical stimulation induces differentiation onset consistent with a therapeutic approach in neuroblastoma cells.Scientific reports · 2026Article
- Fair and Square: Design, Synthesis and Biological Evaluations of Squaric Acid Derivatives as Novel HDAC8 Inhibitors.ChemMedChem · 2026Article
- Targeted HDAC8 inhibition with non-hydroxamate [1,2,4]triazolo[4,3-a] quinoline compounds.Scientific reports · 2026Article
- Differential effects of HDAC8 targeting on Foxp3+ Tregs and effector T cells promote antitumor immunity.JCI insight · 2026Article
- Chemical Perturbations Impacting Histone Acetylation Govern Colorectal Cancer Differentiation.Gastroenterology · 2026Article
- Tumor suppressor network dysregulation in neuroblastoma: molecular mechanisms and precision therapeutic opportunities.Frontiers in cell and developmental biology · 2026Review
- Recent progress in synthetic strategies to develop potent, HDAC8-selective, small-molecule inhibitors.Bioorganic & medicinal chemistry letters · 2025Review
- M344 Suppresses Histone Deacetylase-Associated Phenotypes and Tumor Growth in Neuroblastoma.International journal of molecular sciences · 2025Article
- Interplay Between the Epigenome, the Microenvironment, and the Immune System in Neuroblastoma.Cancers · 2025Review
- Synergistic HDAC4/8 Inhibition Sensitizes Osteosarcoma to Doxorubicin via pAKT/RUNX2 Pathway Modulation.International journal of molecular sciences · 2025Article
- Recent Advancements in the Development of HDAC/Tubulin Dual-Targeting Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Binding mechanism and distant regulation of histone deacetylase 8 by PCI-34051.Communications biology · 2025Article
- Integrative Analysis of Histone Deacetylases Reveals the Potential Role and Prognostic Value of HDAC7 in Hepatocellular Carcinoma.Journal of Cancer · 2025Article
- Lysine deacetylase inhibitors have low selectivity in cells and exhibit predominantly off-target effects.FEBS open bio · 2025Article
- Histone Deacetylase (HDAC) Inhibitors as a Novel Therapeutic Option Against Fibrotic and Inflammatory Diseases.Biomolecules · 2024Review
- Potential role of short-chain fatty acids in the pathogenesis and management of acute lymphocytic leukemia.Annals of translational medicine · 2024Review
36 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
For differentiation-defective malignancies, compounds that modulate transcription, such as retinoic acid and histone deacetylase (HDAC) inhibitors, are of particular interest. HDAC inhibitors are currently under investigation for the treatment of a broad spectrum of cancer diseases. However, one clinical drawback is class-specific toxicity of unselective inhibitors, limiting their full anticancer potential. Selective targeting of individual HDAC isozymes in defined tumor entities may therefore be an attractive alternative treatment approach. We have previously identified HDAC family member 8 (HDAC8) as a novel target in childhood neuroblastoma. Using small-molecule inhibitors, we now demonstrate that selective inhibition of HDAC8 exhibits antineuroblastoma activity without toxicity in two xenograft mouse models of MYCN oncogene-amplified neuroblastoma. In contrast, the unselective HDAC inhibitor vorinostat was more toxic in the same models. HDAC8-selective inhibition induced cell cycle arrest and differentiation in vitro and in vivo. Upon combination with retinoic acid, differentiation was significantly enhanced, as demonstrated by elongated neurofilament-positive neurites and upregulation of NTRK1. Additionally, MYCN oncogene expression was downregulated in vitro and tumor cell growth was markedly reduced in vivo. Mechanistic studies suggest that cAMP-response element-binding protein (CREB) links HDAC8- and retinoic acid-mediated gene transcription. In conclusion, HDAC-selective targeting can be effective in tumors exhibiting HDAC isozyme-dependent tumor growth in vivo and can be combined with differentiation-inducing agents.
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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.