ArticleOncotarget2016
Synergy between histone deacetylase inhibitors and DNA-damaging agents is mediated by histone deacetylase 2 in colorectal cancer.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 35 citations in OpenAlex.
- Pyroptosis as a double-edged sword in colorectal cancer: Molecular mechanisms and therapeutic opportunities.Apoptosis : an international journal on programmed cell death · 2026Review
- Class IIa HDACs forced degradation allows resensitization of oxaliplatin-resistant FBXW7-mutated colorectal cancer.Molecular oncology · 2026Article
- Exploratory Proteomic Profiling Reveals Potential Mediators of 5-FU Response under p53 Deficiency in Colon Cancer Cells.Biomolecules & therapeutics · 2026Article
- Elucidating key targets and mechanisms of diethyl phthalate-induced colorectal cancer through network toxicology and molecular docking.PloS one · 2026Article
- Colorectal Cancer at the Crossroads: The Good, the Bad, and the Future of Platinum-Based Drugs.Chemical reviews · 2025Review
- Mechanisms and Strategies to Overcome Drug Resistance in Colorectal Cancer.International journal of molecular sciences · 2025Review
- DSA-DeepFM: a dual-stage attention-enhanced DeepFM model for predicting anticancer synergistic drug combinations.Bioinformatics advances · 2025Article
- Unlocking Nature's Potential: Ferritin as a Universal Nanocarrier for Amplified Cancer Therapy Testing via 3D Microtissues.ACS applied materials & interfaces · 2024Article
- HDAC2 as a target for developing anti-cancer drugs.Computational and structural biotechnology journal · 2023Review
- The Role of SNHG15 in the Pathogenesis of Hepatocellular Carcinoma.Journal of personalized medicine · 2022Review
- Review
- Acetyl-CoA: An interplay between metabolism and epigenetics in cancer.Frontiers in molecular medicine · 2022Review
- Deacetylation of Transcription Factors in Carcinogenesis.International journal of molecular sciences · 2021Review
- Review
- Characterization of immune responses to anti-PD-1 mono and combination immunotherapy in hematopoietic humanized mice implanted with tumor xenografts.Journal for immunotherapy of cancer · 2019Article
- Expression of LOC285758, a Potential Long Non-coding Biomarker, is Methylation-dependent and Correlates with Glioma Malignancy Grade.Radiology and oncology · 2017Article
- Histone deacetylase inhibitors as cancer therapeutics.Annals of translational medicine · 2016Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Previous studies have associated the overexpression of histone deacetylase 2 (HDAC2) and the presence of TP53 mutations with the progression to advanced stage drug resistant colorectal cancer (CRC). However, the mechanistic link between HDAC2 expression and the TP53 mutational status has remained unexplored. Here, we investigated the function of HDAC2 in drug resistance by assessing the synergistic effects of DNA-targeted chemotherapeutic agents and HDAC inhibitors (HDACis) on two TP53-mutated colorectal adenocarcinoma CRC cell lines (SW480 and HT-29) and on the TP53-wild type carcinoma cell line (HCT116 p53+/+) and its TP53 deficient sub-line (HCT116 p53-/-). We showed that in the untreated SW480 and HT-29 cells the steady-state level of HDAC2 was low compared to a TP53-wild type carcinoma cell line (HCT116 p53+/+). Increased expression of HDAC2 correlated with drug resistance, and depletion by shRNA sensitised the multi-drug resistance cell line HT-29 to CRC chemotherapeutic drugs such as 5-fluorouracil (5-FU) and oxaliplatin (Oxa). Combined treatment with the HDACi suberoylanilide hydroxamic acid plus 5-FU or Oxa reduced the level of HDAC2 expression, modified chromatin structure and induced mitotic cell death in HT-29 cells. Non-invasive bioluminescence imaging revealed significant reductions in xenograft tumour growth with HDAC2 expression level reduced to <50% in treated animals. Elevated levels of histone acetylation on residues H3K9, H4K12 and H4K16 were also found to be associated with resistance to VPA/Dox or SAHA/Dox treatment. Our results suggest that HDAC2 expression rather than the p53 mutation status influences the outcome of combined treatment with a HDACi and DNA-damaging agents in CRC.
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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.