Antiherpetic potential of 6-bromoindirubin-3′-acetoxime (BIO-acetoxime) in human oral epithelial cells
- 257 Downloads
Glycogen synthase kinase 3 (GSK-3) functions in the regulation of glycogen metabolism, in the cell cycle, and in immune responses and is targeted by some viruses to favor the viral life cycle. Inhibition of GSK-3 by 6-bromoindirubin-3′-acetoxime (BIO-acetoxime), a synthetic derivative of a compound from the Mediterranean mollusk Hexaplex trunculus, protects cells from varicella infection. In this study, we examined the effects of BIO-acetoxime against herpes simplex virus-1 (HSV-1) infection in human oral epithelial cells, which represent a natural target cell type. The results revealed that BIO-acetoxime relieves HSV-1-induced cytopathic effects and apoptosis. We also found that BIO-acetoxime reduced viral yields and the expression of different classes of viral proteins. Furthermore, addition of BIO-acetoxime before, simultaneously with or after HSV-1 infection significantly reduced viral yields. Collectively, BIO-acetoxime may suppress viral gene expression and protect oral epithelial cells from HSV-1 infection. These results suggest the possible involvement of GSK-3 in HSV-1 infection.
KeywordsThymidine Kinase Viral Life Cycle Viral Yield Indirubin Oral Epithelial Cell
This investigation was supported by the grant from Ministry of Education, Aim for the Top University Plan and by the Research Grant NSC 101-2314-B-010-033-MY2 from the National Science Council, Taiwan. The authors acknowledge the technical support provided by the Imaging Core Facility of Nanotechnology of the University System of Taiwan-National Yang-Ming University (UST-YMU), especially Pei-Jun Chen and Shu-Fen Lin for their technical support.
- 29.Meijer L, Skaltsounis AL, Magiatis P, Polychronopoulos P, Knockaert M, Leost M, Ryan XP, Vonica CA, Brivanlou A, Dajani R, Crovace C, Tarricone C, Musacchio A, Roe SM, Pearl L, Greengard P (2003) GSK-3-selective inhibitors derived from tyrian purple indirubins. Chem Biol 10:1255–1266PubMedCrossRefGoogle Scholar
- 33.Roizman B, Knipe DM (2001) Herpes simplex viruses and their replication in fields virology, 4 edn. Lippincott, Williams & Wilkins Inc, Philadelphia 2: 2399–2460Google Scholar
- 45.Woodgett JR (2001) Judging a protein by more than its name: GSK-3. Sci STKE 2001:RE12Google Scholar