Suppressive effect of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) on hepatitis C virus replication

Ayami Sato, Yoshimasa Saito, Kazuo Sugiyama, Noriko Sakasegawa, Toshihide Muramatsu, Shinya Fukuda, Mikiko Yoneya, Masaki Kimura, Hirotoshi Ebinuma, Toshifumi Hibi, Masanori Ikeda, Nobuyuki Kato, Hidetsugu Saito

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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 osteopontin (OPN) and down-regulation of apolipoprotein-A1 (Apo-A1) after SAHA treatment. Direct gene induction of OPN and knockdown of Apo-A1 also showed reduction of HCV replication. The liver specific microRNA-122, 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 OPN and Apo-A1 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.

Original languageEnglish
Pages (from-to)1987-1996
Number of pages10
JournalJournal of Cellular Biochemistry
Volume114
Issue number9
DOIs
Publication statusPublished - 2013

Fingerprint

Histone Deacetylase Inhibitors
Virus Replication
Viruses
Hepacivirus
Osteopontin
Apolipoprotein A-I
Liver
Hepatocellular Carcinoma
trichostatin A
Replicon
vorinostat
Virus Diseases
Chronic Hepatitis
Microarray Analysis
Microarrays
MicroRNAs
Epigenomics
Gene expression
Liver Cirrhosis
Toxicity

Keywords

  • APOLIPOPROTEIN-A1
  • HEPATITIS C VIRUS
  • MIR-122
  • OR6
  • OSTEOPONTIN
  • SUBEROYLANILIDE HYDROXAMIC ACID

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Suppressive effect of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) on hepatitis C virus replication. / 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.

In: Journal of Cellular Biochemistry, Vol. 114, No. 9, 2013, p. 1987-1996.

Research output: Contribution to journalArticle

Sato, A, Saito, Y, Sugiyama, K, Sakasegawa, N, Muramatsu, T, Fukuda, S, Yoneya, M, Kimura, M, Ebinuma, H, Hibi, T, Ikeda, M, Kato, N & Saito, H 2013, 'Suppressive effect of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) on hepatitis C virus replication', Journal of Cellular Biochemistry, vol. 114, no. 9, pp. 1987-1996. https://doi.org/10.1002/jcb.24541
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. / Suppressive effect of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) on hepatitis C virus replication. In: Journal of Cellular Biochemistry. 2013 ; Vol. 114, No. 9. pp. 1987-1996.
@article{dcc09c0b3f0349f8962919afbb994be2,
title = "Suppressive effect of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) on hepatitis C virus replication",
abstract = "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 osteopontin (OPN) and down-regulation of apolipoprotein-A1 (Apo-A1) after SAHA treatment. Direct gene induction of OPN and knockdown of Apo-A1 also showed reduction of HCV replication. The liver specific microRNA-122, 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 OPN and Apo-A1 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.",
keywords = "APOLIPOPROTEIN-A1, HEPATITIS C VIRUS, MIR-122, OR6, OSTEOPONTIN, SUBEROYLANILIDE HYDROXAMIC ACID",
author = "Ayami Sato and Yoshimasa Saito and Kazuo Sugiyama and Noriko Sakasegawa and Toshihide Muramatsu and Shinya Fukuda and Mikiko Yoneya and Masaki Kimura and Hirotoshi Ebinuma and Toshifumi Hibi and Masanori Ikeda and Nobuyuki Kato and Hidetsugu Saito",
year = "2013",
doi = "10.1002/jcb.24541",
language = "English",
volume = "114",
pages = "1987--1996",
journal = "Journal of Cellular Biochemistry",
issn = "0730-2312",
publisher = "Wiley-Liss Inc.",
number = "9",

}

TY - JOUR

T1 - Suppressive effect of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) on hepatitis C virus replication

AU - Sato, Ayami

AU - Saito, Yoshimasa

AU - Sugiyama, Kazuo

AU - Sakasegawa, Noriko

AU - Muramatsu, Toshihide

AU - Fukuda, Shinya

AU - Yoneya, Mikiko

AU - Kimura, Masaki

AU - Ebinuma, Hirotoshi

AU - Hibi, Toshifumi

AU - Ikeda, Masanori

AU - Kato, Nobuyuki

AU - Saito, Hidetsugu

PY - 2013

Y1 - 2013

N2 - 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 osteopontin (OPN) and down-regulation of apolipoprotein-A1 (Apo-A1) after SAHA treatment. Direct gene induction of OPN and knockdown of Apo-A1 also showed reduction of HCV replication. The liver specific microRNA-122, 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 OPN and Apo-A1 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.

AB - 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 osteopontin (OPN) and down-regulation of apolipoprotein-A1 (Apo-A1) after SAHA treatment. Direct gene induction of OPN and knockdown of Apo-A1 also showed reduction of HCV replication. The liver specific microRNA-122, 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 OPN and Apo-A1 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.

KW - APOLIPOPROTEIN-A1

KW - HEPATITIS C VIRUS

KW - MIR-122

KW - OR6

KW - OSTEOPONTIN

KW - SUBEROYLANILIDE HYDROXAMIC ACID

UR - http://www.scopus.com/inward/record.url?scp=84881390839&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84881390839&partnerID=8YFLogxK

U2 - 10.1002/jcb.24541

DO - 10.1002/jcb.24541

M3 - Article

VL - 114

SP - 1987

EP - 1996

JO - Journal of Cellular Biochemistry

JF - Journal of Cellular Biochemistry

SN - 0730-2312

IS - 9

ER -