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

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

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

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Singh, S. Aggarwal, B. B. Grunberger, D. Natarajan, K. Burke, T. R.
Description	Author Affiliation: Natarajan K ( Department of Molecular Oncology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.);
Abstract	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 is not known. Since the role of the nuclear factor NF-kappa B in these responses has been documented, we examined the effect of CAPE on this transcription factor. Our results show that the activation of NF-kappa B by tumor necrosis factor (TNF) is completely blocked by CAPE in a dose- and time-dependent manner. Besides TNF, CAPE also inhibited NF-kappa B activation induced by other inflammatory agents including phorbol ester, ceramide, hydrogen peroxide, and okadaic acid. Since the reducing agents reversed the inhibitory effect of CAPE, it suggests the role of critical sulfhydryl groups in NF-kappa B activation. CAPE prevented the translocation of the p65 subunit of NF-kappa B to the nucleus and had no significant effect on TNF-induced I kappa B alpha degradation, but did delay I kappa B alpha resynthesis. The effect of CAPE on inhibition of NF-kappa B binding to the DNA was specific, in as much as binding of other transcription factors including AP-1, Oct-1, and TFIID to their DNA were not affected. When various synthetic structural analogues of CAPE were examined, it was found that a bicyclic, rotationally constrained, 5,6-dihydroxy form was superactive, whereas 6,7-dihydroxy variant was least active. Thus, overall our results demonstrate that CAPE is a potent and a specific inhibitor of NF-kappa B activation and this may provide the molecular basis for its multiple immunomodulatory and antiinflammatory activities.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	17
Volume Number	93
Language	English
Publisher	National Academy of Sciences
Publisher Date	1996-10-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Caffeic Acids Pharmacology I-kappa B Proteins NF-kappa B Antagonists & Inhibitors Phenylethyl Alcohol Analogs & Derivatives Chemistry Cell Line Ceramides DNA-Binding Proteins Metabolism Histiocytes Cytology Molecular Sequence Data Okadaic Acid Phosphorylation Drug Effects Protein Binding Structure-Activity Relationship Tetradecanoylphorbol Acetate Tumor Necrosis Factor-alpha Comparative Study Research Support, Non-U.S. Gov't Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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