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Dual effects of the Nrf2 inhibitor for inhibition of hepatitis C virus and hepatic cancer cells
BACKGROUND: We previously showed that knockdown of nuclear factor E2-related factor 2 (Nrf2) resulted in suppression of hepatitis C virus (HCV) infection. In this study, whether brusatol, an Nrf2 inhibitor, has dual anti-HCV and anticancer effects was explored. METHODS: The anti-HCV effect of brusat...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6019801/ https://www.ncbi.nlm.nih.gov/pubmed/29940898 http://dx.doi.org/10.1186/s12885-018-4588-y |
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author | Murakami, Yuko Sugiyama, Kazuo Ebinuma, Hirotoshi Nakamoto, Nobuhiro Ojiro, Keisuke Chu, Po-sung Taniki, Nobuhito Saito, Yoshimasa Teratani, Toshiaki Koda, Yuzo Suzuki, Takahiro Saito, Kyoko Fukasawa, Masayoshi Ikeda, Masanori Kato, Nobuyuki Kanai, Takanori Saito, Hidetsugu |
author_facet | Murakami, Yuko Sugiyama, Kazuo Ebinuma, Hirotoshi Nakamoto, Nobuhiro Ojiro, Keisuke Chu, Po-sung Taniki, Nobuhito Saito, Yoshimasa Teratani, Toshiaki Koda, Yuzo Suzuki, Takahiro Saito, Kyoko Fukasawa, Masayoshi Ikeda, Masanori Kato, Nobuyuki Kanai, Takanori Saito, Hidetsugu |
author_sort | Murakami, Yuko |
collection | PubMed |
description | BACKGROUND: We previously showed that knockdown of nuclear factor E2-related factor 2 (Nrf2) resulted in suppression of hepatitis C virus (HCV) infection. In this study, whether brusatol, an Nrf2 inhibitor, has dual anti-HCV and anticancer effects was explored. METHODS: The anti-HCV effect of brusatol was investigated by analyzing HCV RNA and proteins in a hepatic cell line persistently-infected with HCV, HPI cells, and by analyzing HCV replication in a replicon-replicating hepatic cell line, OR6 cells. Then, dual anti-HCV and anticancer effects of brusatol and enhancement of the effects by the combination of brusatol with anticancer drugs including sorafenib, which has been reported to have the dual effects, were then investigated. RESULTS: Brusatol suppressed the persistent HCV infection at both the RNA and protein levels in association with a reduction in Nrf2 protein in the HPI cells. Analysis of the OR6 cells treated with brusatol indicated that brusatol inhibited HCV persistence by inhibiting HCV replication. Combination of brusatol with an anticancer drug not only enhanced the anticancer effect but also, in the case of the combination with sorafenib, strongly suppressed HCV infection. CONCLUSIONS: Brusatol has dual anti-HCV and anticancer effects and can enhance the comparable effects of sorafenib. There is therefore the potential for combination therapy of brusatol and sorafenib for HCV-related hepatocellular carcinoma. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-018-4588-y) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6019801 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-60198012018-07-06 Dual effects of the Nrf2 inhibitor for inhibition of hepatitis C virus and hepatic cancer cells Murakami, Yuko Sugiyama, Kazuo Ebinuma, Hirotoshi Nakamoto, Nobuhiro Ojiro, Keisuke Chu, Po-sung Taniki, Nobuhito Saito, Yoshimasa Teratani, Toshiaki Koda, Yuzo Suzuki, Takahiro Saito, Kyoko Fukasawa, Masayoshi Ikeda, Masanori Kato, Nobuyuki Kanai, Takanori Saito, Hidetsugu BMC Cancer Research Article BACKGROUND: We previously showed that knockdown of nuclear factor E2-related factor 2 (Nrf2) resulted in suppression of hepatitis C virus (HCV) infection. In this study, whether brusatol, an Nrf2 inhibitor, has dual anti-HCV and anticancer effects was explored. METHODS: The anti-HCV effect of brusatol was investigated by analyzing HCV RNA and proteins in a hepatic cell line persistently-infected with HCV, HPI cells, and by analyzing HCV replication in a replicon-replicating hepatic cell line, OR6 cells. Then, dual anti-HCV and anticancer effects of brusatol and enhancement of the effects by the combination of brusatol with anticancer drugs including sorafenib, which has been reported to have the dual effects, were then investigated. RESULTS: Brusatol suppressed the persistent HCV infection at both the RNA and protein levels in association with a reduction in Nrf2 protein in the HPI cells. Analysis of the OR6 cells treated with brusatol indicated that brusatol inhibited HCV persistence by inhibiting HCV replication. Combination of brusatol with an anticancer drug not only enhanced the anticancer effect but also, in the case of the combination with sorafenib, strongly suppressed HCV infection. CONCLUSIONS: Brusatol has dual anti-HCV and anticancer effects and can enhance the comparable effects of sorafenib. There is therefore the potential for combination therapy of brusatol and sorafenib for HCV-related hepatocellular carcinoma. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-018-4588-y) contains supplementary material, which is available to authorized users. BioMed Central 2018-06-25 /pmc/articles/PMC6019801/ /pubmed/29940898 http://dx.doi.org/10.1186/s12885-018-4588-y Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Murakami, Yuko Sugiyama, Kazuo Ebinuma, Hirotoshi Nakamoto, Nobuhiro Ojiro, Keisuke Chu, Po-sung Taniki, Nobuhito Saito, Yoshimasa Teratani, Toshiaki Koda, Yuzo Suzuki, Takahiro Saito, Kyoko Fukasawa, Masayoshi Ikeda, Masanori Kato, Nobuyuki Kanai, Takanori Saito, Hidetsugu Dual effects of the Nrf2 inhibitor for inhibition of hepatitis C virus and hepatic cancer cells |
title | Dual effects of the Nrf2 inhibitor for inhibition of hepatitis C virus and hepatic cancer cells |
title_full | Dual effects of the Nrf2 inhibitor for inhibition of hepatitis C virus and hepatic cancer cells |
title_fullStr | Dual effects of the Nrf2 inhibitor for inhibition of hepatitis C virus and hepatic cancer cells |
title_full_unstemmed | Dual effects of the Nrf2 inhibitor for inhibition of hepatitis C virus and hepatic cancer cells |
title_short | Dual effects of the Nrf2 inhibitor for inhibition of hepatitis C virus and hepatic cancer cells |
title_sort | dual effects of the nrf2 inhibitor for inhibition of hepatitis c virus and hepatic cancer cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6019801/ https://www.ncbi.nlm.nih.gov/pubmed/29940898 http://dx.doi.org/10.1186/s12885-018-4588-y |
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