The anti-herpetic activity of trichosanthin via the nuclear factor-κB and p53 pathways.

AIMS

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.

MAIN METHODS

The western blot, electrophoretic mobility shift assay, chromatin immunoprecipitation assay, enzyme-linked immunosorbent assay and cytokinesis-block micronucleus were applied in this study.

KEY FINDINGS

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.

SIGNIFICANCE

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.