| abstract |
Nuclear Factor NF-λB is a protein specific to B cells, binds to a specific DNA sequence within the immunoglobin light chain λ locus enhancer region, and plays a central role in various responses, due to rapid induction of gene expression. NF-λB controls the expression of various inflammatory cytokines, the major histocompatibility complex genes, and adhesion molecules involved in tumor metastasis. The present invention is drawn to the inhibition of activation of NF-λB by caffeic acid phenethyl ester (CAPE) and two analogues of CAPE. Tumor necrosis factor (TNF) activation of NF-λB is completely blocked by CAPE in a dose- and time-dependent manner, as is activation by phorbol ester, ceramide, hydrogen peroxide, and okadaic acid. Additionally, capsaicin (8-methyl-N-vanillyl-6-nonenamide) and resiniferatoxin inhibit the activation of NF-λB induced by different agents. Further, the present invention discloses methods for using these inhibitors in the treatment of pathological conditions caused by the activation of NF-λB, such as toxic shock, acute inflammatory conditions, acute phase response, atherosclerosis and cancer. |