標題: Sulforaphane Suppresses Hepatitis C Virus Replication by Up-Regulating Heme Oxygenase-1 Expression through PI3K/Nrf2 Pathway
作者: Yu, Jung-Sheng
Chen, Wei-Chun
Tseng, Chin-Kai
Lin, Chun-Kuang
Hsu, Yao-Chin
Chen, Yen-Hsu
Lee, Jin-Ching
生醫工程研究所
Institute of Biomedical Engineering
公開日期: 29-Mar-2016
摘要: Hepatitis C virus (HCV) infection-induced oxidative stress is a major risk factor for the development of HCV-associated liver disease. Sulforaphane (SFN) is an antioxidant phytocompound that acts against cellular oxidative stress and tumorigenesis. However, there is little known about its anti-viral activity. In this study, we demonstrated that SFN significantly suppressed HCV protein and RNA levels in HCV replicon cells and infectious system, with an IC50 value of 5.7 +/- 0.2 mu M. Moreover, combination of SFN with anti-viral drugs displayed synergistic effects in the suppression of HCV replication. In addition, we found nuclear factor erythroid 2-related factor 2 (Nrf2)/HO-1 induction in response to SFN and determined the signaling pathways involved in this process, including inhibition of NS3 protease activity and induction of IFN response. In contrast, the anti-viral activities were attenuated by knockdown of HO-1 with specific inhibitor (SnPP) and shRNA, suggesting that anti-HCV activity of SFN is dependent on HO-1 expression. Otherwise, SFN stimulated the phosphorylation of phosphoinositide 3-kinase (PI3K) leading Nrf2-mediated HO-1 expression against HCV replication. Overall, our results indicated that HO-1 is essential in SFN-mediated anti-HCV activity and provide new insights in the molecular mechanism of SFN in HCV replication.
URI: http://dx.doi.org/10.1371/journal.pone.0152236
http://hdl.handle.net/11536/133462
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0152236
期刊: PLOS ONE
Volume: 11
Issue: 3
起始頁: 0
結束頁: 0
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