title: The anti-herpetic activity of trichosanthin via the nuclear factor-κB and p53 pathways.
abstract: OBJECTIVE
  Trichosanthin (TCS) is a type I ribosome-inactivating protein. We have previously shown that TCS induces a more potent apoptosis in infected cells over uninfected cells, but the mechanism underlying it is unclear. In this study, we explored the anti-HSV-1 mechanism of TCS through the nuclear factor-κB (NF-κB) and p53 pathways in human epithelial carcinoma (HEp-2) cells with wild type p53.
  
  
  METHODS
  The western blot, electrophoretic mobility shift assay, chromatin immunoprecipitation assay, enzyme-linked immunosorbent assay and cytokinesis-block micronucleus were applied in this study.
  
  
  RESULTS
  It was shown that TCS inhibited the HSV-1-induced NF-κB activation. Meanwhile, in HSV-1 infected cells, TCS treatment activated significantly more p53 and BAX, with no DNA damage and less S phase arrest compared with uninfected cells. The activation of BAX in infected cells correlated with the cell death signaling of p53.
  
  
  CONCLUSIONS
  Taken together, these results suggest that the anti-HSV-1 effect of TCS is related to its suppression of NF-κB activation and regulation of p53-dependent cell death in infected cells.
authors.affiliation: The Key laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, Wuxi, China.
authors.forename: Dongxu
authors.initials: D
authors.lastname: He
authors.forename: Yongtang
authors.initials: Y
authors.lastname: Zheng
authors.forename: Siucheung
authors.initials: S
authors.lastname: Tam
mesh_terms: D000998:Antiviral Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000187:drug effects; D004847:Epithelial Cells / Q000821:virology; D006561:Herpes Simplex / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D018259:Herpesvirus 1, Human / Q000187:drug effects*; D006801:Humans; D016328:NF-kappa B / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects; D029778:Trichosanthes / Q000737:chemistry*; D015978:Trichosanthin / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014779:Virus Replication / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D016328:NF-kappa B; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D015978:Trichosanthin