Inhibition of histone acetyltransferase activity by anacardic acid sensitizes tumor cells to ionizing radiation

• DOI: 10.1016/j.febslet.2006.06.092
• Publication Date: 2006-07-11T14:01:21Z
• Authors: Yingli Sun; Xiaofeng Jiang; Shujuan Chen; Brendan D. Price
• Keywords: Radiation-Sensitizing Agents; 0303 health sciences; Tumor Suppressor Proteins; DNA repair; Anacardic acid; Cell Cycle Proteins; Ataxia Telangiectasia Mutated Proteins; DNA-Activated Protein Kinase; Protein Serine-Threonine Kinases; Lysine Acetyltransferase 5; Anacardic Acids; Radiosensitivity; DNA-Binding Proteins; 03 medical and health sciences; Tip60; ATM; Cell Line, Tumor; Neoplasms; Radiation, Ionizing; HAT; Humans; Enzyme Inhibitors; HeLa Cells; Histone Acetyltransferases

Histone acetyltransferases (HATs) regulate transcription, chromatin structure and DNA repair. Here, we utilized a novel HAT inhibitor, anacardic acid, to examine the role of HATs in the DNA damage response. Anacardic acid inhibits the Tip60 HAT in vitro, and blocks the Tip60‐dependent activation of the ATM and DNA–PKcs protein kinases by DNA damage in vivo. Further, anacardic acid sensitizes human tumor cells to the cytotoxic effects of ionizing radiation. These results demonstrate a central role for HATs such as Tip60 in regulating the DNA damage response. HAT inhibitors provide a novel therapeutic approach for increasing the sensitivity of tumors to radiation therapy.