ArticleRadiation oncology (London, England)2012
DNMT (DNA methyltransferase) inhibitors radiosensitize human cancer cells by suppressing DNA repair activity.
Article in Radiation oncology (London, England), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 122 citations in OpenAlex.
- Compound Library Screening Identified Cladribine as a Novel Radiosensitizer for Prostate Cancer.Cancer science · 2026Article
- DNA methyltransferase inhibitors in oncology: clinical progress, limitations and future directions.Epigenomics · 2026Review
- A New Look at the Role of Radiation-Related Epigenetic Mechanisms in Diagnosis and Anticancer Therapies.Cells · 2025Review
- Article
- Changes in the Level of DNA Methylation inInternational journal of molecular sciences · 2023Article
- The Importance of M1-and M2-Polarized Macrophages in Glioma and as Potential Treatment Targets.Brain sciences · 2023Review
- Marine Invertebrates: A Promissory Still Unexplored Source of Inhibitors of Biomedically Relevant Metallo Aminopeptidases Belonging to the M1 and M17 Families.Marine drugs · 2023Review
- Intrinsic sexual dimorphism in the placenta determines the differential response to benzene exposure.iScience · 2023Article
- Lineage plasticity and treatment resistance in prostate cancer: the intersection of genetics, epigenetics, and evolution.Frontiers in endocrinology · 2023Review
- Prospects and feasibility of synergistic therapy with radiotherapy, immunotherapy, and DNA methyltransferase inhibitors in non-small cell lung cancer.Frontiers in immunology · 2023Review
- The DNA Double-Strand Break Repair in Glioma: Molecular Players and Therapeutic Strategies.Molecular neurobiology · 2022Review
- Inhibitors of DNA Methylation.Advances in experimental medicine and biology · 2022Review
- Radioresistance in rhabdomyosarcomas: Much more than a question of dose.Frontiers in oncology · 2022Review
- Enhancement of Radiosensitivity by DNA Hypomethylating Drugs through Apoptosis and Autophagy in Human Sarcoma Cells.Biomolecules & therapeutics · 2022Article
- Expression of 5-methylcytosine regulators is highly associated with the clinical phenotypes of prostate cancer and DNMTs expression predicts biochemical recurrence.Cancer medicine · 2021Article
- Bioactive Compounds with Antiglioma Activity from Marine Species.Biomedicines · 2021Review
- Hydralazine and Panobinostat Attenuate Malignant Properties of Prostate Cancer Cell Lines.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Perspectives and controversies regarding the use of natural products for the treatment of lung cancer.Cancer medicine · 2021Review
- Aberrant methylation of GADD45A is associated with decreased radiosensitivity in cervical cancer through the PI3K/AKT signaling pathway.Oncology letters · 2021Article
- Epigenetic Mechanisms in DNA Double Strand Break Repair: A Clinical Review.Frontiers in molecular biosciences · 2021Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHistone modifications and DNA methylation are two major factors in epigenetic phenomenon. Unlike the histone deacetylase inhibitors, which are known to exert radiosensitizing effects, there have only been a few studies thus far concerning the role of DNA methyltransferase (DNMT) inhibitors as radiosensitizers. The principal objective of this study was to evaluate the effects of DNMT inhibitors on the radiosensitivity of human cancer cell lines, and to elucidate the mechanisms relevant to that process.
methodsA549 (lung cancer) and U373MG (glioblastoma) cells were exposed to radiation with or without six DNMT inhibitors (5-azacytidine, 5-aza-2'-deoxycytidine, zebularine, hydralazine, epigallocatechin gallate, and psammaplin A) for 18 hours prior to radiation, after which cell survival was evaluated via clonogenic assays. Cell cycle and apoptosis were analyzed via flow cytometry. Expressions of DNMT1, 3A/3B, and cleaved caspase-3 were detected via Western blotting. Expression of γH2AX, a marker of radiation-induced DNA double-strand break, was examined by immunocytochemistry.
resultsPretreatment with psammaplin A, 5-aza-2'-deoxycytidine, and zebularine radiosensitized both A549 and U373MG cells. Pretreatment with psammaplin A increased the sub-G1 fraction of A549 cells, as compared to cells exposed to radiation alone. Prolongation of γH2AX expression was observed in the cells treated with DNMT inhibitors prior to radiation as compared with those treated by radiation alone.
conclusionsPsammaplin A, 5-aza-2'-deoxycytidine, and zebularine induce radiosensitivity in both A549 and U373MG cell lines, and suggest that this effect might be associated with the inhibition of DNA repair.
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