Involvement of HDAC1 and the PI3K/PKC signaling pathways in NF-kB activation by the HDAC inhibitor apicidin
- Authors
- Kim, Yong Kee; Dong-Wan Seo; Dong-Won Kang; Hoi Young Lee; Jeung-Whan Han; Su-Nam Kim
- Issue Date
- Sep-2006
- Publisher
- Academic Press Inc. Elsevier Science
- Citation
- Biochemical and Biophysical Research Communications, v.347, no.4, pp 1088 - 1093
- Pages
- 6
- Journal Title
- Biochemical and Biophysical Research Communications
- Volume
- 347
- Number
- 4
- Start Page
- 1088
- End Page
- 1093
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/146265
- DOI
- 10.1016/j.bbrc.2006.06.196
- ISSN
- 0006-291X
1090-2104
- Abstract
- Histone deacetylase (HDAC) inhibitors are appreciated as one of promising anticancer drugs, but they exert differential responses depending on the cell type. We recently reported the critical role of NF-kappa B as a modulator in determining cell fate for apoptosis in response to an HDAC inhibitor. In this study, we investigate a possible signaling pathway required for NF-kappa B activation in response to the HDAC inhibitor apicidin. Treatment of HeLa cells with apicidin leads to an increase in transcriptional activity of NF-kappa B and the expression of its target genes, IL-8 and TNF-alpha. TNF-alpha expression by apicidin is induced at earlier time points than NF-kappa B activation or IL-8 expression. In addition, our data show that the early expression of TNF-alpha does not lead to activation of NF-kappa B, because disruption of TNF-alpha activity by a neutralizing antibody does not affect nuclear translocation of NF-kappa B, I kappa B alpha degradation or reporter gene activation by apicidin. However, this activation of NF-kappa B requires the PI3K and PKC signaling pathways, but not ERK or JNK. Furthermore, apicidin activation of NF-kappa B seems to result from HDAC1 inhibition, as evidenced by the observation that overexpression of HDAC1, but not HDAC2, 3 or 4, dramatically inhibits NF-kappa B reporter gene activity. Collectively, our results suggest that activation of NF-kappa B signaling by apicidin requires both the PI3K/PKC signaling pathways and HDAC1, and functions as a critical modulator in determining the cellular effect of apicidin. (c) 2006 Elsevier Inc. All rights reserved.
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