title: Silymarin enhanced cytotoxic effect of anti-Fas agonistic antibody CH11 on A375-S2 cells.
abstract: Silymarin is a polyphenolic flavonoid from milk thistle (Silybum marianum), which has anti-inflammatory, cytoprotective as well as antioxidant effects. Our previous study demonstrated that silymarin has anti-apoptotic effect against UV irradiation. In this study, we assessed the effect of silymarin on anti-Fas agonistic antibody CH11-treated human malignant melanoma, A375-S2 cells. Pretreatment with silymarin (3 x 10(- 4) mol/L) significantly induced cell apoptosis in CH11-treated A375-S2 cells. Mitochondrial transmembrane potential (DeltaPsi(m)) was also down-regulated by silymarin pretreatment. Caspase-8, -9, -3 and pan-caspase inhibitors partially reversed silymarin-induced apoptosis of CH11-treated cells. The expression of Fas-associated proteins with death domain (FADD), a downstream molecule of the death receptor pathway, was increased by silymarin pretreatment, followed by cleavage of procaspase-8, whose activation induced cell apoptosis. Moreover, cleavage of procaspase-3 and digestion of its substrate, the inhibitor of caspase-activated DNase (ICAD), were also increased by silymarin pretreatment. These results suggested that silymarin could also exaggerate the apoptotic effect of anti-Fas agonistic antibody CH11 on A375-S2 cells.
authors.affiliation: China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang, China.
authors.forename: Lin-Hao
authors.initials: LH
authors.lastname: Li
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Wu
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Jiang
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Tashiro
authors.forename: Satoshi
authors.initials: S
authors.lastname: Onodera
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Uchiumi
authors.forename: Takashi
authors.initials: T
authors.lastname: Ikejima
mesh_terms: D000906:Antibodies / Q000276:immunology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D012838:Silymarin / Q000494:pharmacology*; D019014:fas Receptor / Q000276:immunology*
chemical_list: D000906:Antibodies; D012838:Silymarin; D019014:fas Receptor