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Title: Kushenin induces the apoptosis of HCV-infected cells by blocking the PI3K-Akt-mTOR pathway via inhibiting NS5A

Abstract

With the increased burden induced by HCV, there is an urgent need to develop better-tolerated agents with good safety. In this study, we evaluated the anti-HCV capability of kushenin, as well as the possible mechanism to Huh7.5-HCV cells. The results demonstrated that kushenin significantly inhibited the HCV-RNA level. Similarly, the expression of HCV-specific protein NS5A was also decreased. Molecular docking results displayed that kushenin bonded well to the active pockets of HCV NS5A, further confirming the effects of kushenin on HCV replication. Coimmunoprecipitation assay determined that kushenin suppressed the interaction between PI3K and NS5A in HCV-replicon cells. Furthermore, kushenin exerted an obviously induced function on HCV-replicon cells apoptosis by inhibiting PI3K-Akt-mTOR pathway, which could be ameliorated by the specific activator IGF-1 addition. Taken together, kushenin possesses the ability to inhibit HCV replication, and contributes to the increased apoptosis of HCV-infected cells by blocking the PI3K-Akt-mTOR pathway via inhibiting NS5A. Our results provide important evidence for a better understanding of the pathogenesis of HCV infection, and suggest that kushenin has the potential to treat HCV disease. - Highlights: • Kushenin inhibits HCV replication. • Kushenin bonds directly to NS5A protein. • Kushenin induces the apoptosis of HCV-infected cells. • kushenin suppressesmore » the interaction between PI3K and NS5A. • Kushenin inhibits PI3K-Akt-mTOR pathway.« less

Authors:
; ; ;  [1];  [2];  [1]
  1. Department of Infectious Diseases, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061 (China)
  2. School of Pharmacy, Xi’an Jiaotong University, Xi’an, Shaanxi 710061 (China)
Publication Date:
OSTI Identifier:
22648590
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 345; Journal Issue: 1; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; CHANNELING; DISEASES; FUNCTIONS; INTERACTIONS; PATHOGENESIS; PROTEINS; REPLICONS; RNA; SAFETY

Citation Formats

Zhou, Yi, Chen, Na, Liu, Xiaojing, Lin, Shumei, Luo, Wenjuan, E-mail: wenjuanluoxa@163.com, and Liu, Min, E-mail: minliusx@163.com. Kushenin induces the apoptosis of HCV-infected cells by blocking the PI3K-Akt-mTOR pathway via inhibiting NS5A. United States: N. p., 2016. Web. doi:10.1016/J.YEXCR.2016.05.002.
Zhou, Yi, Chen, Na, Liu, Xiaojing, Lin, Shumei, Luo, Wenjuan, E-mail: wenjuanluoxa@163.com, & Liu, Min, E-mail: minliusx@163.com. Kushenin induces the apoptosis of HCV-infected cells by blocking the PI3K-Akt-mTOR pathway via inhibiting NS5A. United States. doi:10.1016/J.YEXCR.2016.05.002.
Zhou, Yi, Chen, Na, Liu, Xiaojing, Lin, Shumei, Luo, Wenjuan, E-mail: wenjuanluoxa@163.com, and Liu, Min, E-mail: minliusx@163.com. Fri . "Kushenin induces the apoptosis of HCV-infected cells by blocking the PI3K-Akt-mTOR pathway via inhibiting NS5A". United States. doi:10.1016/J.YEXCR.2016.05.002.
@article{osti_22648590,
title = {Kushenin induces the apoptosis of HCV-infected cells by blocking the PI3K-Akt-mTOR pathway via inhibiting NS5A},
author = {Zhou, Yi and Chen, Na and Liu, Xiaojing and Lin, Shumei and Luo, Wenjuan, E-mail: wenjuanluoxa@163.com and Liu, Min, E-mail: minliusx@163.com},
abstractNote = {With the increased burden induced by HCV, there is an urgent need to develop better-tolerated agents with good safety. In this study, we evaluated the anti-HCV capability of kushenin, as well as the possible mechanism to Huh7.5-HCV cells. The results demonstrated that kushenin significantly inhibited the HCV-RNA level. Similarly, the expression of HCV-specific protein NS5A was also decreased. Molecular docking results displayed that kushenin bonded well to the active pockets of HCV NS5A, further confirming the effects of kushenin on HCV replication. Coimmunoprecipitation assay determined that kushenin suppressed the interaction between PI3K and NS5A in HCV-replicon cells. Furthermore, kushenin exerted an obviously induced function on HCV-replicon cells apoptosis by inhibiting PI3K-Akt-mTOR pathway, which could be ameliorated by the specific activator IGF-1 addition. Taken together, kushenin possesses the ability to inhibit HCV replication, and contributes to the increased apoptosis of HCV-infected cells by blocking the PI3K-Akt-mTOR pathway via inhibiting NS5A. Our results provide important evidence for a better understanding of the pathogenesis of HCV infection, and suggest that kushenin has the potential to treat HCV disease. - Highlights: • Kushenin inhibits HCV replication. • Kushenin bonds directly to NS5A protein. • Kushenin induces the apoptosis of HCV-infected cells. • kushenin suppresses the interaction between PI3K and NS5A. • Kushenin inhibits PI3K-Akt-mTOR pathway.},
doi = {10.1016/J.YEXCR.2016.05.002},
journal = {Experimental Cell Research},
number = 1,
volume = 345,
place = {United States},
year = {Fri Jul 01 00:00:00 EDT 2016},
month = {Fri Jul 01 00:00:00 EDT 2016}
}