Suppressive effect of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) on hepatitis C virus replication. Issue 9 (18th July 2013)

• Record Type: Journal Article
• Authors: Sato, Ayami; Saito, Yoshimasa; Sugiyama, Kazuo; Sakasegawa, Noriko; Muramatsu, Toshihide; Fukuda, Shinya; Yoneya, Mikiko; Kimura, Masaki; Ebinuma, Hirotoshi; Hibi, Toshifumi; Ikeda, Masanori; Kato, Nobuyuki; Saito, Hidetsugu
• Is Part Of: Journal of cellular biochemistry. Volume 114:Issue 9(2013:Sep.)
• Page Start: 1987
• Page End: 1996
• Publication Date: 2013-07-18
• Subjects: Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.24541
• Languages: English
• ISSNs: 0730-2312

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="jcb24541-sec-0001" sec-type="section"> <p>The histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) has a clinical promise for treatment of cancer including hepatocellular carcinoma (HCC). To investigate effect of SAHA on hepatitis C virus (HCV) replication, we treated the HCV replicon cell OR6 with SAHA. HCV replication was significantly inhibited by SAHA at concentrations below 1 μM with no cellular toxicity. Another HDAC inhibitor, tricostatin A, also showed reduction of HCV replication. The microarray analysis and quantitative RT‐PCR demonstrated up‐regulation of <italic>osteopontin</italic> (<italic>OPN</italic>) and down‐regulation of <italic>apolipoprotein‐A1</italic> (<italic>Apo‐A1</italic>) after SAHA treatment. Direct gene induction of <italic>OPN</italic> and knockdown of <italic>Apo‐A1</italic> also showed reduction of HCV replication. The liver specific <italic>microRNA‐122</italic>, which is involved in HCV replication, was not affected by SAHA treatment. These results suggest that SAHA has suppressive effect on HCV replication through alterations of gene expression such as <italic>OPN</italic> and <italic>Apo‐A1</italic> in host cells. Epigenetic treatment with HDAC inhibitors may be a novel therapeutic approach for diseases associated with HCV infection such as chronic hepatitis, liver cirrhosis, and HCC. J. Cell. Biochem. 114: 1987–1996, 2013. © 2013 Wiley Periodicals, Inc.</p> </sec> </abstract>