Epigallocatechin-3-gallate, a histone acetyltransferase inhibitor, inhibits EBV-induced B lymphocyte transformation via suppression of RelA acetylation

Kyung Chul Choi, Gu Jung Myung, Yoo Hyun Lee, Chun Yoon Joo, Hyun Kwon Seung, Hee Bum Kang, Mi Jeong Kim, Jeong Heon Cha, Jun Kim Young, Jin Jun Woo, Myun Lee Jae, Ho Geun Yoon

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Abstract

Because the p300/CBP-mediated hyperacetylation of RelA (p65) is critical for nuclear factor-κB (NF-κB) activation, the attenuation of p65 acetylation is a potential molecular target for the prevention of chronic inflammation. During our ongoing screening study to identify natural compounds with histone acetyltransferase inhibitor (HATi) activity, we identified epigallocatechin-3-gallate (EGCG) as a novel HATi with global specificity for the majority of HAT enzymes but with no activity toward epigenetic enzymes including HDAC, SIRT1, and HMTase. At a dose of 100 μmol/L, EGCG abrogates p300-induced p65 acetylation in vitro and in vivo, increases the level of cytosolic IκBα, and suppresses tumor necrosis factor α (TNFα)-induced NF-κB activation. We also showed that EGCG prevents TNFα-induced p65 translocation to the nucleus, confirming that hyperacetylation is critical for NF-κB translocation as well as activity. Furthermore, EGCG treatment inhibited the acetylation of p65 and the expression of NF-κB target genes in response to diverse stimuli. Finally, EGCG reduced the binding of p300 to the promoter region of interleukin-6 gene with an increased recruitment of HDAC3, which highlights the importance of the balance between HATs and histone deacetylases in the NF-κB-mediated inflammatory signaling pathway. Importantly, EGCG at 50 μmol/L dose completely blocks EBV infection-induced cytokine expression and subsequently the EBV-induced B lymphocyte transformation. These results show the crucial role of acetylation in the development of inflammatory-related diseases.

Original languageEnglish
Pages (from-to)583-592
Number of pages10
JournalCancer Research
Volume69
Issue number2
DOIs
Publication statusPublished - 2009 Jan 15

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Choi, K. C., Myung, G. J., Lee, Y. H., Joo, C. Y., Seung, H. K., Kang, H. B., Kim, M. J., Cha, J. H., Young, J. K., Woo, J. J., Jae, M. L., & Yoon, H. G. (2009). Epigallocatechin-3-gallate, a histone acetyltransferase inhibitor, inhibits EBV-induced B lymphocyte transformation via suppression of RelA acetylation. Cancer Research, 69(2), 583-592. https://doi.org/10.1158/0008-5472.CAN-08-2442