Selective inhibition of NF-kappaB activation by the flavonoid hepatoprotector silymarin in HepG2. Evidence for different activating pathways.
The bioflavonoid silymarin is found to potently suppress both nuclear factor kappa-B (NF-kappaB)-DNA binding activity and its dependent gene expression induced by okadaic acid in the hepatoma cell line HepG2. Surprisingly, tumor necrosis factor-alpha-induced NF-kappaB activation was not affected by silymarin, thus demonstrating a pathway-dependent inhibition by silymarin. Many genes encoding the proteins of the hepatic acute phase response are under the control of the transcription factor NF-kappaB, a key regulator in the inflammatory and immune reactions. Thus, the inhibitory effect of silymarin on NF-kappaB activation could be involved in its hepatoprotective property.
Saliou
C
C
Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA.
Rihn
B
B
Cillard
J
J
Okamoto
T
T
Packer
L
L
D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D017930:Genes, Reporter; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019319:Okadaic Acid / Q000494:pharmacology; D020011:Protective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D012838:Silymarin / Q000494:pharmacology* / Q000627:therapeutic use; D013755:Tetradecanoylphorbol Acetate; D014162:Transfection; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D008070:Lipopolysaccharides; D016328:NF-kappa B; D020011:Protective Agents; D012838:Silymarin; D014409:Tumor Necrosis Factor-alpha; D019319:Okadaic Acid; D004247:DNA; D013755:Tetradecanoylphorbol Acetate