Caffeic acid phenethyl ester is a potent and specific inhibitor of activation of nuclear transcription factor NF-kappa B.

• DOI: 10.1073/pnas.93.17.9090
• Publication Date: 2002-07-26T14:40:52Z
• Authors: K Natarajan; S Singh; T R Burke; D Grunberger; B B Aggarwal
• Keywords: 0303 health sciences; Base Sequence; Tumor Necrosis Factor-alpha; Molecular Sequence Data; NF-kappa B; Histiocytes; Phenylethyl Alcohol; Ceramides; Cell Line; DNA-Binding Proteins; Structure-Activity Relationship; 03 medical and health sciences; Caffeic Acids; NF-KappaB Inhibitor alpha; Okadaic Acid; Humans; Tetradecanoylphorbol Acetate; I-kappa B Proteins; Phosphorylation; Protein Binding

Caffeic acid phenethyl ester (CAPE), an active component of propolis from honeybee hives, is known to have antimitogenic, anticarcinogenic, antiinflammatory, and immunomodulatory properties. The molecular basis for these diverse properties not known. Since the role nuclear factor NF-kappa B in responses has been documented, we examined effect CAPE on this transcription factor. Our results show that activation by tumor necrosis (TNF) completely blocked a dose- time-dependent manner. Besides TNF, also inhibited induced other inflammatory agents including phorbol ester, ceramide, hydrogen peroxide, okadaic acid. reducing reversed inhibitory CAPE, it suggests critical sulfhydryl groups activation. prevented translocation p65 subunit nucleus had no significant TNF-induced I kappa alpha degradation, but did delay resynthesis. inhibition binding DNA was specific, as much factors AP-1, Oct-1, TFIID their were affected. When various synthetic structural analogues examined, found bicyclic, rotationally constrained, 5,6-dihydroxy form superactive, whereas 6,7-dihydroxy variant least active. Thus, overall our demonstrate potent specific inhibitor may provide its multiple antiinflammatory activities.