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Suppression of autophagy by mycophenolic acid contributes to inhibition of HCV replication in human hepatoma cells.

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  • معلومة اضافية
    • المصدر:
      Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
    • بيانات النشر:
      Original Publication: London : Nature Publishing Group, copyright 2011-
    • الموضوع:
      Autophagy/*drug effects ; Carcinoma, Hepatocellular/*metabolism ; Hepacivirus/*physiology ; Liver Neoplasms/*metabolism ; Mycophenolic Acid/*pharmacology ; Neoplasm Proteins/*metabolism ; Virus Replication/*drug effects; Carcinoma, Hepatocellular/pathology ; Carcinoma, Hepatocellular/virology ; Cell Line, Tumor ; Humans ; Liver Neoplasms/pathology ; Liver Neoplasms/virology
    • نبذة مختصرة :
      Previous studies have shown that mycophenolic acid (MPA) has an anti-HCV activity. However, the mechanism of MPA-mediated inhibition of HCV replication remains to be determined. This study investigated whether MPA has an effect on autophagy, a cellular machinery required for HCV replication, thereby, inhibits HCV replication in Huh7 cells. MPA treatment of Huh7 cells could suppress autophagy, evidenced by decreased LC3B-II level and conversion of LC3B-I to LC3B-II, decreased autophagosome formation, and increased p62 level compared to MPA-untreated cells. Tunicamycin treatment or HCV infection could induce cellular autophagy, however, MPA also exhibited its inhibitory effect on tunicamycin- or HCV infection-induced autophagy. The expression of three autophagy-related genes, Atg3, Atg5, and Atg7 were identified to be inhibited by MPA treatment. Over-expression of these genes could partly recover HCV replication inhibited by MPA; however, silencing their expression by siRNAs could enhance the inhibitory effect of MPA on HCV. Collectively, these results reveal that suppression of autophagy by MPA plays a role in its anti-HCV activity. Down-regulating the expression of three autophagy-related genes by MPA involves in its antiviral mechanism.
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    • الرقم المعرف:
      0 (Neoplasm Proteins)
      HU9DX48N0T (Mycophenolic Acid)
    • الموضوع:
      Date Created: 20170310 Date Completed: 20181108 Latest Revision: 20181113
    • الموضوع:
      20231215
    • الرقم المعرف:
      PMC5343675
    • الرقم المعرف:
      10.1038/srep44039
    • الرقم المعرف:
      28276509