| abstract |
The present invention provides an inhibitor of NF-kB, guggulsterone and its analogs. Guggulsterone suppresses NF-KB activation induced by TNF, phorbol ester, okadaic acid, cigarette smoke, H202 and IL-1β, as well as constitutive NF-kB activation expressed in most tumor cells. One mechanism by which guggulsterone inhibits activation of NF-kB is through suppression of IkBα phosphorylation and IkBα degradation. NF-kB-dependent gene transcription is modulated by guggulsterone and its analogs. In particular, induction by TNF, TNFR1, TRADD, TRAF2, NIK and IKK, is modulated by guggulsterone and its analogs. In addition, guggulsterone decreased the expression of genes involved in anti-apoptosis (IAP1, XIAP, Bfl-1/A1, bcl-2, cFLIP, survivin), proliferation (cyclin Dl, c-myc) and metastasis (MMP-9, COX2 and VEGF). |