ArticleFrontiers in oncology2021
Evaluation of Histone Deacetylase Inhibitors as Radiosensitizers for Proton and Light Ion Radiotherapy.
Article in Frontiers in oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 10 citations in OpenAlex.
- Spirohydantoin derivatives exert dopamine DScientific reports · 2026Article
- Largazole targets Musashi protein expression via miR-125b-5p and sensitizes triple-negative breast cancer cells to radiation.Frontiers in pharmacology · 2026Article
- 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
- Radiotherapy in bone sarcoma: the quest for better treatment option.BMC cancer · 2023Review
- The Cellular Response to Complex DNA Damage Induced by Ionising Radiation.International journal of molecular sciences · 2023Review
- Biological Mechanisms to Reduce Radioresistance and Increase the Efficacy of Radiotherapy: State of the Art.International journal of molecular sciences · 2022Review
- The DNA Double-Strand Break Repair in Glioma: Molecular Players and Therapeutic Strategies.Molecular neurobiology · 2022Review
- A toolbox for class I HDACs reveals isoform specific roles in gene regulation and protein acetylation.PLoS genetics · 2022Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Significant opportunities remain for pharmacologically enhancing the clinical effectiveness of proton and carbon ion-based radiotherapies to achieve both tumor cell radiosensitization and normal tissue radioprotection. We investigated whether pretreatment with the hydroxamate-based histone deacetylase inhibitors (HDACi) SAHA (vorinostat), M344, and PTACH impacts radiation-induced DNA double-strand break (DSB) induction and repair, cell killing, and transformation (acquisition of anchorage-independent growth in soft agar) in human normal and tumor cell lines following gamma ray and light ion irradiation. Treatment of normal NFF28 primary fibroblasts and U2OS osteosarcoma, A549 lung carcinoma, and U87MG glioma cells with 5-10 µM HDACi concentrations 18 h prior to cesium-137 gamma irradiation resulted in radiosensitization measured by clonogenic survival assays and increased levels of colocalized gamma-H2AX/53BP1 foci induction. We similarly tested these HDACi following irradiation with 200 MeV protons, 290 MeV/n carbon ions, and 350 MeV/n oxygen ions delivered in the Bragg plateau region. Unlike uniform gamma ray radiosensitization, effects of HDACi pretreatment were unexpectedly cell type and ion species-dependent with C-12 and O-16 ion irradiations showing enhanced G0/G1-phase fibroblast survival (radioprotection) and in some cases reduced or absent tumor cell radiosensitization. DSB-associated foci levels were similar for proton-irradiated DMSO control and SAHA-treated fibroblast cultures, while lower levels of induced foci were observed in SAHA-pretreated C-12 ion-irradiated fibroblasts. Fibroblast transformation frequencies measured for all radiation types were generally LET-dependent and lowest following proton irradiation; however, both gamma and proton exposures showed hyperlinear transformation induction at low doses (≤25 cGy). HDACi pretreatments led to overall lower transformation frequencies at low doses for all radiation types except O-16 ions but generally led to higher transformation frequencies at higher doses (>50 cGy). The results of these
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