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Open AccessArticle

Histone Deacetylase Inhibitor Induced Radiation Sensitization Effects on Human Cancer Cells after Photon and Hadron Radiation Exposure

Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki Prefecture 305-8575, Japan
Department of Environmental & Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523, USA
Department of Basic Medical Sciences for Radiation Damages, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Chiba Prefecture 263-8555, Japan
Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(2), 496;
Received: 11 January 2018 / Revised: 29 January 2018 / Accepted: 2 February 2018 / Published: 7 February 2018
(This article belongs to the Special Issue Advances and Challenges in Biomolecular Radiation Research)
Suberoylanilide hydroxamic acid (SAHA) is a histone deacetylase inhibitor, which has been widely utilized throughout the cancer research field. SAHA-induced radiosensitization in normal human fibroblasts AG1522 and lung carcinoma cells A549 were evaluated with a combination of γ-rays, proton, and carbon ion exposure. Growth delay was observed in both cell lines during SAHA treatment; 2 μM SAHA treatment decreased clonogenicity and induced cell cycle block in G1 phase but 0.2 μM SAHA treatment did not show either of them. Low LET (Linear Energy Transfer) irradiated A549 cells showed radiosensitization effects on cell killing in cycling and G1 phase with 0.2 or 2 μM SAHA pretreatment. In contrast, minimal sensitization was observed in normal human cells after low and high LET radiation exposure. The potentially lethal damage repair was not affected by SAHA treatment. SAHA treatment reduced the rate of γ-H2AX foci disappearance and suppressed RAD51 and RPA (Replication Protein A) focus formation. Suppression of DNA double strand break repair by SAHA did not result in the differences of SAHA-induced radiosensitization between human cancer cells and normal cells. In conclusion, our results suggest SAHA treatment will sensitize cancer cells to low and high LET radiation with minimum effects to normal cells. View Full-Text
Keywords: proton; carbon ions; SAHA proton; carbon ions; SAHA
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MDPI and ACS Style

Gerelchuluun, A.; Maeda, J.; Manabe, E.; Brents, C.A.; Sakae, T.; Fujimori, A.; Chen, D.J.; Tsuboi, K.; Kato, T.A. Histone Deacetylase Inhibitor Induced Radiation Sensitization Effects on Human Cancer Cells after Photon and Hadron Radiation Exposure. Int. J. Mol. Sci. 2018, 19, 496.

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