ArticleInternational journal of molecular sciences2023
Synergistic Interaction of the Class IIa HDAC Inhibitor CHDI0039 with Bortezomib in Head and Neck Cancer Cells.
Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 5 citations in OpenAlex.
- Bridging the gap: a genetically validated avian chorioallantoic membrane platform for investigation of spontaneous circulating tumor cells.Molecular oncology · 2026Article
- Unraveling the molecular landscape: an overview on gene expression, epigenetic alterations, and therapeutic challenges in head and neck squamous cell carcinoma.Molecular genetics and genomics : MGG · 2026Review
- HDAC inhibitors in cancer therapy: sensitization mechanisms, combination strategies, and translational challenges.Frontiers in cell and developmental biology · 2026Review
- HDAC4/5 Inhibitor, LMK-235 Improves Animal Voluntary Movement in MPTP-Induced Parkinson's Disease Model.Pharmacology research & perspectives · 2025Article
- Synthesis and biological evaluation ofJournal of enzyme inhibition and medicinal chemistry · 2024Article
- Targeting histone deacetylases in head and neck squamous cell carcinoma: molecular mechanisms and therapeutic targets.Journal of translational medicine · 2024Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
In contrast to class I/IIb/pan histone deacetylase inhibitors (HDACi), the role of class IIa HDACi as anti-cancer chemosensitizing agents is less well understood. Here, we studied the effects of HDAC4 in particular and the class IIa HDACi CHDI0039 on proliferation and chemosensitivity in Cal27 and cisplatin-resistant Cal27CisR head and neck squamous cell cancer (HNSCC). HDAC4 and HDAC5 overexpression clones were generated. HDAC4 overexpression (Cal27_HDAC4) increased proliferation significantly compared to vector control cells (Cal27_VC). Chicken chorioallantoic membrane (CAM) studies confirmed the in vitro results: Cal27_HDAC4 tumors were slightly larger than tumors from Cal27_VC, and treatment with CHDI0039 resulted in a significant decrease in tumor size and weight of Cal27_HDAC4 but not Cal27_VC. Unlike class I/pan-HDACi, treatment with CHDI0039 had only a marginal impact on cisplatin cytotoxicity irrespective of HDAC4 and HDAC5 expression. In contrast, the combination of CHDI0039 with bortezomib was synergistic (Chou-Talalay) in MTT and caspase 3/7 activation experiments. RNAseq indicated that treatment with CHDI0039 alters the expression of genes whose up- or downregulation is associated with increased survival in HNSCC patients according to Kaplan-Meier data. We conclude that the combination of class IIa HDACi with proteasome inhibitors constitutes an effective treatment option for HNSCC, particularly for platinum-resistant cancers.
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