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Gallic acid suppresses lipopolysaccharide-induced nuclear factor-kappaB signaling by preventing RelA acetylation in A549 lung cancer cells

Authors
 Kyung-Chul Choi  ;  Yoo-Hyun Lee  ;  Myung Gu Jung  ;  Seung Hyun Kwon  ;  Mi-Jeong Kim  ;  Woo Jin Jun  ;  Jeongmin Lee  ;  Jae Myun Lee  ;  Ho-Geun Yoon 
Citation
 Molecular Cancer Research, Vol.7(12) : 2011-2021, 2009 
Journal Title
 Molecular Cancer Research 
ISSN
 1541-7786 
Issue Date
2009
Abstract
Although multiple studies have revealed that gallic acid plays an important role in the inhibition of malignant transformation, cancer development, and inflammation, the molecular mechanism of gallic acid in inflammatory diseases is still unclear. In this study, we identified gallic acid from Rosa rugosa as a histone acetyltransferase (HAT) inhibitor with global specificity for the majority of HAT enzymes, but with no activity toward epigenetic enzymes including sirtuin (silent mating type information regulation 2 homologue) 1 (S. cerevisiae), histone deacetylase, and histone methyltransferase. Enzyme kinetic studies indicated that gallic acid uncompetitively inhibits p300/CBP-dependent HAT activities. We found that gallic acid inhibits p300-induced p65 acetylation, both in vitro and in vivo, increases the level of cytosolic IkappaBalpha, prevents lipopolysaccharide (LPS)-induced p65 translocation to the nucleus, and suppresses LPS-induced nuclear factor-kappaB activation in A549 lung cancer cells. We have also shown that gallic acid treatment inhibits the acetylation of p65 and the LPS-induced serum levels of interleukin-6 in vivo. Importantly, gallic acid generally inhibited inflammatory responses caused by other stimuli, including LPS, IFN-gamma, and interleukin-1beta, and further downregulated the expression of nuclear factor-kappaB-regulated antiapoptotic genes. These results show the crucial role of acetylation in the development of inflammatory diseases.
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DOI
10.1158/1541-7786.MCR-09-0239
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
권승현(Kwon, Seung Hyun)
김미정(Kim, Mi Jeong) ORCID logo https://orcid.org/0000-0002-0758-7145
윤호근(Yoon, Ho Geun) ORCID logo https://orcid.org/0000-0003-2718-3372
이재면(Lee, Jae Myun) ORCID logo https://orcid.org/0000-0002-5273-3113
최경철(Choi, Kyung Chul)
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/105459
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