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.