title: Glycyrrhizin inhibits TNF-induced, but not Fas-mediated, apoptosis in the human hepatoblastoma line HepG2.
abstract: To determine the transaminase-lowering action of glycyrrhizin (GL) immunologically, the effect of GL on tumor necrosis factor (TNF)-alpha- and Fas-mediated apoptosis was assessed using a human hepatoblastoma line, HepG2 cells. The HepG2 cells were resistant to TNF-alpha and anti-Fas antibody, but were rendered susceptible to TNF-alpha and anti-Fas antibody in the presence of actinomycin D (Act D), an inhibitor of RNA synthesis. The cytotoxicity induced by TNF-alpha/Act D or anti-Fas/Act D was accompanied by DNA fragmentation, indicating apoptotic death of HepG2 cells. GL partially prevented the apoptosis of HepG2 cells induced by TNF-alpha/Act D in a GL-dose dependent fashion. However, this protective effect of GL was not observed in the cytotoxicity of HepG2 caused by anti-Fas/Act D. Although the protection mechanism of GL, observed in a limited fashion against TNF-alpha-mediated apoptosis, is unclear, the present results provide an immunological explanation for the transaminase-lowering action of GL in the GL treatment of chronic liver diseases involving apoptotic hepatocyte death in their pathogenesis.
authors.affiliation: Department of Parasitology, Nara Medical University, Kashihara, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yoshikawa
authors.forename: M
authors.initials: M
authors.lastname: Toyohara
authors.forename: S
authors.initials: S
authors.lastname: Ueda
authors.forename: A
authors.initials: A
authors.lastname: Shiroi
authors.forename: H
authors.initials: H
authors.lastname: Takeuchi
authors.forename: T
authors.initials: T
authors.lastname: Nishiyama
authors.forename: T
authors.initials: T
authors.lastname: Yamada
authors.forename: H
authors.initials: H
authors.lastname: Fukui
authors.forename: S
authors.initials: S
authors.lastname: Ishizaka
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D000906:Antibodies; D017209:Apoptosis; D019695:Glycyrrhizic Acid / Q000494:pharmacology*; D018197:Hepatoblastoma; D006801:Humans; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000502:physiology*; D019014:fas Receptor / Q000276:immunology / Q000502:physiology*
chemical_list: D000890:Anti-Infective Agents; D000906:Antibodies; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D019695:Glycyrrhizic Acid