Kim, Yong Kee Seo, Dong-Wan Kang, Dong-Won Lee, Hoi Young Han, Jeung-Whan Kim, Su-Nam 2024-01-21T02:31:20Z 2024-01-21T02:31:20Z 2021-09-01 2006-09-08 0006-291X https://pubs.kist.re.kr/handle/201004/135131 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. English ACADEMIC PRESS INC ELSEVIER SCIENCE HISTONE DEACETYLASE INHIBITOR SP1 SITES ACETYLATION EXPRESSION TRANSCRIPTION CHROMATIN CELLS GENE P21(WAF1/CIP1) APOPTOSIS Involvement of HDAC1 and the PI3K/PKC signaling pathways in NF-kappa B activation by the HDAC inhibitor apicidin Article 10.1016/j.bbrc.2006.06.196 1 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.347, no.4, pp.1088 - 1093 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 347 4 1088 1093 scie scopus 000239681100034 2-s2.0-33746380872 Biochemistry & Molecular Biology Biophysics Biochemistry & Molecular Biology Biophysics Article HISTONE DEACETYLASE INHIBITOR SP1 SITES ACETYLATION EXPRESSION TRANSCRIPTION CHROMATIN CELLS GENE P21(WAF1/CIP1) APOPTOSIS histone deacetylase HDAC inhibitor apicidin NF-kappa B PI3K PKC