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Updated: Jun 12, 2026

Assays for Validating Histone Acetyltransferase Inhibitors
Published on: August 6, 2020
HDAC inhibitor-mediated radiosensitization in human carcinoma cells: a general phenomenon?
In Ah Kim1, Il Han Kim, Hak Jae Kim
1Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea.
Abstract:
Histone deacetylase inhibitors (HDIs) have attracted considerable attention for anticancer therapy strategy, including radiosensitization. Regarding a potential application of HDI as a radiosensitizer in the treatment of solid tumors, an important question is whether treatment efficacy would be influenced by intrinsic differences between cancer cells, such as different histologic origin and status of ATM or p53. First we have observed the in vitro radiosensitization by Trichostatin A (TSA) on the broad spectrum of human tumor cell lines having different histologic origin such as HCT116 adenocarcinoma of colon, A549 adenocarcinoma of lung, HN-3 squamous cell carcinoma of head/neck, and HeLa squamous carcinoma of uterine cervix, using clonogenic assay. Next, we have systematically assessed the radiosensitization on the cell lines having different ATM or p53 status. We found that pretreatment of HDI consistently resulted in radiosensitization of all cell lines tested, though the sensitizer enhancement ratio of individual cell lines was variable. We also observed that TSA-mediated radiosensitization was clearly influenced by p53 and ATM status of cells tested. The data presented here indicate that HDI enhances the radiation induced cell killing in the various cancer cells having intrinsic differences and may serve as a general strategy for enhancing tumor cell radiosensitivity. These results have potential implications for the clinical utility of HDI in increasing the anticancer efficacy of radiation.
Insights
Histone deacetylase inhibitors (HDIs) enhance radiation therapy
Area of Science:
- Oncology
- Molecular Biology
- Radiotherapy
Background:
- Histone deacetylase inhibitors (HDIs) are investigated for cancer therapy, particularly as radiosensitizers.
- Understanding how cancer cell heterogeneity affects HDI radiosensitization is crucial for clinical application.
Purpose of the Study:
- To evaluate the radiosensitizing effect of Trichostatin A (TSA), a HDI, across diverse human cancer cell lines.
- To determine if p53 and ATM gene status influence TSA-mediated radiosensitization.
Main Methods:
- In vitro radiosensitization was assessed using clonogenic assays.
- Multiple human cancer cell lines with varying histologic origins and p53/ATM statuses were utilized.
- Trichostatin A (TSA) was used as the HDI radiosensitizer.
Main Results:
- TSA consistently demonstrated radiosensitization across all tested cancer cell lines.
- The degree of radiosensitization varied among cell lines.
- TSA-mediated radiosensitization was significantly influenced by the p53 and ATM status of the cells.
Conclusions:
- HDIs, like TSA, can enhance radiation-induced cancer cell killing, suggesting a potential general strategy for improving radiotherapy efficacy.
- The effectiveness of HDI radiosensitization is modulated by intrinsic cancer cell characteristics, including p53 and ATM status.
- These findings support the potential clinical utility of HDIs in combination with radiation therapy for solid tumors.
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