Conversion of trichosanthin-induced CD95 (Fas) type I into type II apoptotic signaling during Herpes simplex virus infection

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

“…Although the indiscriminate killing of host cells would certainly inhibit viral replication, a compound can only be considered as an antiviral agent when it selectively kills infected cells. Our previous and current studies have demonstrated that TCS is significantly more toxic to HSV-1-infected Vero (Huang et al, 2006) and HEp-2 cells (He et al, 2011) (Fig. 1) than to uninfected cells.…”

“…When TCS suppresses the NF-κB pathway induced by HSV-1 infection, it may weaken the viral ability to evade the host cell cellular antiviral response and to oppose apoptosis-inducing stimuli. According to our previous (Huang et al, 2006;Zheng et al, 2001) and current (He et al, 2011) studies, the anti-HSV-1 effect of TCS is mediated by cytotoxicity, by decreasing the viability and increasing the apoptosis of infected cells. In HEp-2 cells (Fig.…”

“…It is probably because in TCS treated and HSV-1 infected cells, besides the phosphorylation of p53, the p53 is also stabilized by tumor suppressor protein p14 ARF . The p14 ARF activation is often connected to the mitochondrial mediated apoptosis pathway, which happens in HSV-1 infected cells treated with TCS (He et al, 2011). Therefore, when p14 ARF inhibits the activity of MDM2 and sequesters MDM2 into the nucleolus (Ashcroft and Vousden, 1999), MDM2 level could be down regulated, TCS thus promoting p53 activity.…”

“…Moreover, ACV-resistant viral strains may arise in immunocompromised patients; therefore, it is necessary to develop additional agents that inhibit HSV via different mechanisms. Our previous studies have demonstrated that TCS inhibits HSV-1 replication through a different mechanism than ACV (He and Tam, 2010) and that the anti-HSV-1 activity of TCS is related to its selective cytotoxicity toward HSV-1-infected cells (Zheng et al, 2001;Huang et al, 2006;He et al, 2011). Nevertheless, the mechanism by which TCS selectively targets infected cells remains unclear.…”

Bioactive proteins and peptides isolated from Chinese medicines with pharmaceutical potential

“…TCS suppressed nasopharyngeal carcinomas via inhibiting Notch signaling and proliferation in vitro [115], as well as induced cell death and inhibited telomerase activity in nude mice [116]. Moreover, TCS possessed anti-HSV-1 property in human epithelial carcinoma cell line HEp-2 via type II apoptotic signaling after infection [117], and inhibiting the activation of NF-κB and inducing p53-dependent apoptosis [118]. TCS was used to successfully cure 85% of 140 cases of ectopic pregnancy with higher beta-human chorionic gonadotropin [119].…”