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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
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.
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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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