Histone deacetylase inhibitors enhance phosphorylation of histone H2AX after ionizing radiation
- Division of Molecular Oncology and Molecular Diagnosis, Graduate School of Medicine, Sapporo Medical University, Sapporo, Hokkaido (Japan)
- Division of Molecular Oncology and Molecular Diagnosis, Graduate School of Medicine, Sapporo Medical University, Sapporo, Hokkaido (Japan) and First Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Hokkaido (Japan)
- Department of Radiology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido (Japan)
- First Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Hokkaido (Japan)
Purpose Histone deacetylase (HDAC) inhibitors are believed to be promising radiosensitizers. To explore their effects on ionizing radiation (IR), we examined whether the HDAC inhibitors m-carboxycinnamic acid bis-hydroxamide (CBHA) and depsipeptide FK228 affect H2AX phosphorylation ({gamma}-H2AX), a landmark of DNA double-strand breaks after IR exposure. Methods and Materials We evaluated the effects of the HDAC inhibitors on clonogenic assay in human lung carcinoma A549 cells and progression of A549 xenograft tumors. IR-induced DNA damage was evaluated by histone {gamma}-H2AX. Histone hyperacetylation was induced by overexpression of histone acetyltransferase p300 and evaluated by Western blots. Results M-carboxycinnamic acid bishydroxyamide pretreatment radiosensitized A549 cells and strongly inhibited A549 xenograft tumor progression. CBHA and FK228, but not 5-fluorouracil, enhanced IR-induced {gamma}-H2AX in A549 and other cancer cell lines. Overexpression of p300 similarly augmented IR-induced {gamma}-H2AX. Conclusion The results of this study suggest that HDAC inhibitors enhance IR-induced {gamma}-H2AX, most likely through histone hyperacetylation, and radiosensitize various cancers.
- OSTI ID:
- 20842920
- Journal Information:
- International Journal of Radiation Oncology, Biology and Physics, Vol. 65, Issue 3; Other Information: DOI: 10.1016/j.ijrobp.2006.03.019; PII: S0360-3016(06)00402-0; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0360-3016
- Country of Publication:
- United States
- Language:
- English
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