Role of the Fas/Fas ligand death receptor pathway in ginseng saponin metabolite-induced apoptosis in HepG2 cells.
This research team found in previous studies, that the ginseng saponin metabolite IH901 induces apoptosis in HepG2 cells via a mitochondrial-mediated pathway, which resulted in the activation of caspase-9 and subsequently of caspase-3 and -8. Based on these results, the involvement of the Fas/Fas ligand (FasL) death-receptor pathway, in IH901-induced apoptosis in HepG2 cells, was investigated. Levels of Fas and the Fas ligand (FasL) mRNA or protein were not increased by IH901, rather they were decreased significantly at 18 h post treatment. Soluble FasL (sFasL) was detectable by immunoprecipitation analysis in the medium of HepG2 cells treated with IH901. Increased levels of sFasL were inversely correlated with the levels of FasL. Preincubation of HepG2 cells with antagonistic anti-Fas antibody showed little protective effect, if any, on IH901-induced cell death. At a 30 microM (24 and 48 h) and 40 microM (24 h) concentration of IH901, the cytotoxic effect of IH901 was less then 50%, anti-Fas antibody prevented IH901-induced cell death. However, at a 60 microM (24 and 48 h) and 40 microM (48 h) concentration of IH901, cell death rates were about 80% or more and most of the chemopreventive and chemotherapeutic effects of IH901 were manifested. Blocking the Fas receptor did not influence IH901-induced cell death. These results indicate that the Fas/FasL system is engaged, but not required for IH901-induced cell death, at pharmacologically significant concentrations.
Oh
Seon-Hee
SH
College of Pharmacy and Medicinal Resources Research Center, Wonkwang University, Iksan, Jeonbuk 570-749, Korea.
Yin
Hu-Quan
HQ
Lee
Byung-Hoon
BH
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D053222:Fas Ligand Protein; D006801:Humans; D008024:Ligands; D008562:Membrane Glycoproteins / Q000502:physiology*; D005894:Panax / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D012502:Sapogenins / Q000378:metabolism / Q000494:pharmacology; D012503:Saponins / Q000378:metabolism / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D019014:fas Receptor / Q000378:metabolism / Q000502:physiology*
C482402:20-O-(beta-D-glucopyranosyl)-20(S)-protopanaxadiol; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008024:Ligands; D008562:Membrane Glycoproteins; D018124:Receptors, Tumor Necrosis Factor; D012502:Sapogenins; D012503:Saponins; D019014:fas Receptor