INHIBITION OF NF-KAPPA-B ACTIVATION BY PANEPOXYDONE

In a search for new inhibitors of NF-kappa B mediated signal transduct ion in COS-7 cells using the Secreted Alkaline Phosphatase as reporter gene, panepoxydone has been isolated from fermentations of the basidi omycete Lentinus crinitus. Panepoxydone inhibits the NF-kappa B activa ted expression of the SEAP with an IC50 of 1.5 - 2 mu g/ml (7.15 - 9.5 2 mu M). NO inhibition of AP-1 mediated expression of the reporter gen e could be observed at a concentration up to 5 mu g/ml panepoxydone. P anepoxydone strongly reduced the TPA, TNF-alpha and ocadaic acid media ted binding of NF-kappa B to the high affinity consensus sequence in C OS-7 and HeLa S3 cells as confirmed by EMSA's. Panepoxydone inhibits t he I kappa B phosphorylation and therfore sequesteres the NF-kappa B c omplex in an inactive form. (C) 1996 Academic Press, Inc.