Inhibition of NF-kappa B activation by panepoxydone.
In a search for new inhibitors of NF-kappa B mediated signal transduction in COS-7 cells using the Secreted Alkaline Phosphatase as reporter gene, panepoxydone has been isolated from fermentations of the basidiomycete Lentinus crinitus. Panepoxydone inhibits the NF-kappa B activated expression of the SEAP with an IC50 of 1.5-2 micrograms/ml (7.15-9.52 microM). No inhibition of AP-1 mediated expression of the reporter gene could be observed at a concentration up to 5 micrograms/ml panepoxydone. Panepoxydone strongly reduced the TPA, TNF-alpha and ocadaic acid mediated binding of NF-kappa B to the high affinity consensus sequence in COS-7 and HeLa S3 cells as confirmed by EMSA's. Panepoxydone inhibits the I kappa B phosphorylation and therefore sequesteres the NF-kappa B complex in an inactive form.
Erkel
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G
Lehrbereich Biotechnologie der Universität, Kaiserslautern, Germany. erkel@rhrk.uni-kl.de
Anke
T
T
Sterner
O
O
D000469:Alkaline Phosphatase / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D002460:Cell Line; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009838:Oligodeoxyribonucleotides; D010957:Plasmids
D019086:Bridged Bicyclo Compounds, Heterocyclic; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; C101349:panepoxydone; D000469:Alkaline Phosphatase