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

Abstract	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.
Authors	Yingli Sun, Xiaofeng Jiang, Shujuan Chen, Brendan D Price
Journal	FEBS letters (FEBS Lett) Vol. 580 Issue 18 Pg. 4353-6 (Aug 07 2006) ISSN: 0014-5793 [Print] England
PMID	16844118 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	Anacardic Acids Cell Cycle Proteins DNA-Binding Proteins Enzyme Inhibitors Radiation-Sensitizing Agents Tumor Suppressor Proteins anacardic acid Histone Acetyltransferases KAT5 protein, human Lysine Acetyltransferase 5 ATM protein, human Ataxia Telangiectasia Mutated Proteins DNA-Activated Protein Kinase Protein Serine-Threonine Kinases
Topics	Anacardic Acids (pharmacology, therapeutic use) Ataxia Telangiectasia Mutated Proteins Cell Cycle Proteins (antagonists & inhibitors) Cell Line, Tumor DNA-Activated Protein Kinase (antagonists & inhibitors) DNA-Binding Proteins (antagonists & inhibitors) Enzyme Inhibitors (pharmacology, therapeutic use) HeLa Cells Histone Acetyltransferases (antagonists & inhibitors) Humans Lysine Acetyltransferase 5 Neoplasms (radiotherapy) Protein Serine-Threonine Kinases (antagonists & inhibitors) Radiation, Ionizing Radiation-Sensitizing Agents Tumor Suppressor Proteins (antagonists & inhibitors)

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