Histone deacetylase inhibitors enhance phosphorylation of histone H2AX after ionizing radiation

作者：Zhang Y; Adachi M^*; Zou H; Hareyama M; Imai K; Shinomura Y

来源：International Journal of Radiation Oncology, Biology, Physics, 2006, 65(3): 859-866.

DOI：10.1016/j.ijrobp.2006.03.019

• histone deacetylase inhibitor
• ionizing radiation
• histone H2AX
• DNA damage

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.

• 出版日期2006-7-1