Cancer Research and Treatment

Original Article

Sequence-Dependent Radiosensitization of Histone Deacetylase Inhibitors Trichostatin A and SK-7041: Jin Ho Kim, Il Han Kim, Jin Hee Shin, Hak Jae Kim, In Ah Kim; Cancer Res Treat. 2013;45(4):334-342. Published online December 31, 2013; DOI: https://doi.org/10.4143/crt.2013.45.4.334

PURPOSE
This preclinical study is to determine whether the capacity of histone deacetylase (HDAC) inhibitors to enhance radiation response depends on temporal sequences of HDAC inhibition and irradiation.
MATERIALS AND METHODS
The effects of HDAC inhibitors trichostatin A (TSA) and SK-7041 on radiosensitivity in human lung cancer cells were examined using a clonogenic assay, exposing cells to HDAC inhibitors in various sequences of HDAC inhibition and radiation. We performed Western blot of acetylated histone H3 and flow cytometry to analyze cell cycle phase distribution.
RESULTS
TSA and SK-7041 augmented radiation cell lethality in an exposure time-dependent manner when delivered before irradiation. The impact of TSA and SK-7041 on radiosensitivity rapidly diminished when HDAC inhibition was delayed after irradiation. Radiation induced the acetylation of histone H3 in cells exposed to TSA, while irradiation alone had no effect on the expression of acetylated histone H3 in TSA-naive cells. Preirradiation exposure to TSA abrogated radiation-induced G2/M-phase arrest. When delivered after irradiation, TSA had no effect on the peak of radiation-induced G2/M-phase arrest.
CONCLUSION
TSA and SK-7041 enhances radiosensitivity only when delivered before irradiation. Unless proven otherwise, it seems prudent to apply scheduling including preirradiation HDAC inhibition so that maximal radiosensitization is obtained.

Citations

Citations to this article as recorded by

Mechanistic Sequence of Histone Deacetylase Inhibitors and Radiation Treatment: An Overview
Elsie Neo Seane, Shankari Nair, Charlot Vandevoorde, Anna Joubert
Pharmaceuticals.2024; 17(5): 602. CrossRef
Investigation of geroprotective and radioprotective effects of berberine and trichostatin A on the model of Drosophila melanogaster
N. Ulyasheva, E. Proshkina, M. Shaposhnikov, A. Moskalev
Proceedings of the Komi Science Centre of the Ural Division of the Russian Academy of Sciences.2023; 0(6): 93. CrossRef
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Radiation Research.2021;[Epub] CrossRef
Time-sequential change in immune-related gene expression after irradiation in glioblastoma: next-generation sequencing analysis
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Cancer Research and Treatment.2019; 51(2): 696. CrossRef
Psammaplin A-Modified Novel Radiosensitizers for Human Lung Cancer and Glioblastoma Cells
Chan Woo Wee, Jin Ho Kim, Hak Jae Kim, Hyun-Cheol Kang, Soo Youn Suh, Beom Soo Shin, Eunsook Ma, Il Han Kim
Journal of Radiation Protection and Research.2019; 44(1): 15. CrossRef
Isotype-Specific Inhibition of Histone Deacetylases: Identification of Optimal Targets for Radiosensitization
Jin Ho Kim, Sung Ho Moon, Mina No, Jae Jin Kim, Eun Jung Choi, Bong Jun Cho, Jae Sung Kim, Il Han Kim, In Ah Kim
Cancer Research and Treatment.2016; 48(3): 1130. CrossRef

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