ArticleProceedings of the National Academy of Sciences of the United States of America2010
Histone deacetylase inhibitor induces DNA damage, which normal but not transformed cells can repair.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 197 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
197 citing papers in PubMed, 1 synthesis or guideline pooled it, 377 citations in OpenAlex.
- Drug repurposing based on differentially expressed genes suggests drug combinations with possible synergistic effects in treatment of lung adenocarcinoma.Cancer biology & therapy · 2023Pooled it
- Clinical Trials Assessing Hypomethylating Agents Combined with Other Therapies: Causes for Failure and Potential Solutions.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Trial
- The PEMDAC phase 2 study of pembrolizumab and entinostat in patients with metastatic uveal melanoma.Nature communications · 2021Trial
- Oral tetrahydrouridine and decitabine for non-cytotoxic epigenetic gene regulation in sickle cell disease: A randomized phase 1 study.PLoS medicine · 2017Trial
- A phase I/II trial of the histone deacetylase inhibitor romidepsin for adults with recurrent malignant glioma: North American Brain Tumor Consortium Study 03-03.Neuro-oncology · 2011Trial
- Bortezomib interacts synergistically with belinostat in human acute myeloid leukaemia and acute lymphoblastic leukaemia cells in association with perturbations in NF-κB and Bim.British journal of haematology · 2011Trial
- Advances in Somatostatin Receptor-Targeting Peptide Receptor Radionuclide Therapy for Neuroendocrine Tumors: Biological Rationale, Combination Strategies, and Clinical Perspectives.International journal of molecular sciences · 2026Review
- Multimodal radiosensitization by hafnium oxide nanoparticles and HDAC inhibitors: mechanistic insights.Nanoscale advances · 2026Article
- HDAC inhibitors in cancer therapy: sensitization mechanisms, combination strategies, and translational challenges.Frontiers in cell and developmental biology · 2026Review
- High-throughput screening identifies the activity of histone deacetylase inhibitors in patient-derived models of soft tissue sarcoma.Cancer biology & therapy · 2025Article
- Histone deacetylase inhibitors sensitize glioblastoma models to temozolomide and reprogram immunosuppressive myeloid cells.Scientific reports · 2025Article
- Epigenetic drugs in cancer therapy.Cancer metastasis reviews · 2025Review
- A phase I study of MLN4924 and belinostat in relapsed/refractory acute myeloid leukemia or myelodysplastic syndrome.Cancer chemotherapy and pharmacology · 2025Article
- Multi-Target Inhibitor CUDC-101 Impairs DNA Damage Repair and Enhances Radiation Response in Triple-Negative Breast Cell Line.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Mechanistic Sequence of Histone Deacetylase Inhibitors and Radiation Treatment: An Overview.Pharmaceuticals (Basel, Switzerland) · 2024Review
- New synergistic combination therapy approaches with HDAC inhibitor quisinostat, cisplatin or PARP inhibitor talazoparib for urothelial carcinoma.Journal of cellular and molecular medicine · 2024Article
- The impact of selective HDAC inhibitors on the transcriptome of early mouse embryos.BMC genomics · 2024Article
- Reversion from basal histone H4 hypoacetylation at the replication fork increases DNA damage in FANCA deficient cells.PloS one · 2024Article
- Histone deacetylases: potential therapeutic targets for idiopathic pulmonary fibrosis.Frontiers in cell and developmental biology · 2024Review
- Quisinostat is a brain-penetrant radiosensitizer in glioblastoma.JCI insight · 2023Article
137 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Histone deacetylase inhibitors (HDACi) developed as anti-cancer agents have a high degree of selectivity for killing cancer cells. HDACi induce acetylation of histones and nonhistone proteins, which affect gene expression, cell cycle progression, cell migration, and cell death. The mechanism of the tumor selective action of HDACi is unclear. Here, we show that the HDACi, vorinostat (Suberoylanilide hydroxamic acid, SAHA), induces DNA double-strand breaks (DSBs) in normal (HFS) and cancer (LNCaP, A549) cells. Normal cells in contrast to cancer cells repair the DSBs despite continued culture with vorinostat. In transformed cells, phosphorylated H2AX (gammaH2AX), a marker of DNA DSBs, levels increased with continued culture with vorinostat, whereas in normal cells, this marker decreased with time. Vorinostat induced the accumulation of acetylated histones within 30 min, which could alter chromatin structure-exposing DNA to damage. After a 24-h culture of cells with vorinostat, and reculture without the HDACi, gammaH2AX was undetectable by 2 h in normal cells, while persisting in transformed cells for the duration of culture. Further, we found that vorinostat suppressed DNA DSB repair proteins, e.g., RAD50, MRE11, in cancer but not normal cells. Thus, the HDACi, vorinostat, induces DNA damage which normal but not cancer cells can repair. This DNA damage is associated with cancer cell death. These findings can explain, in part, the selectivity of vorinostat in causing cancer cell death at concentrations that cause little or no normal cell death.
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Registered trials
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.