Enhanced Radiation-Induced Cell Killing and Prolongation of γH2AX Foci Expression by the Histone Deacetylase Inhibitor MS-275

摘要: Histone deacetylase (HDAC) inhibitors are undergoing clinical evaluation for cancer therapy. Because HDAC modulates chromatin structure and gene expression, parameters considered to influence radioresponse, we have investigated the effects of inhibitor MS-275 on radiosensitivity two human tumor cell lines (DU145 prostate carcinoma U251 glioma). Acetylation status histones H3 H4 was determined as a function time after addition removal from culture medium. acetylation increased by 6 h addition, reaching maximum between 24 48 exposure; providing fresh drug-free medium then resulted in decrease histone that began approached untreated levels 16 h. Treatment cells with followed irradiation had little or no effect radiation-induced death. However, exposure before an increase dose enhancement factors 1.9 1.3 DU145 cells, respectively. This treatment protocol did not result redistribution into more radiosensitive phase cycle apoptosis. modify course γH2AX expression irradiated cells. Whereas there significant difference foci at h, number expressing significantly greater MS-275-treated irradiation. These results indicate can enhance suggest this may involve inhibition DNA repair.