Abstract
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 μM.
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.
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