Substituted trans-stilbenes can inhibit or enhance the TPA-induced up-regulation of activator protein-1.
BACKGROUND
The activator protein-1 (AP-1) family of transcription factors contributes to regulation of numerous genes involved in proliferation, apoptosis, and tumorigenesis. A wide array of stimuli can activate AP-1, including pro-inflammatory cytokines, growth factors, tumor promoters and stress. Numerous plant polyphenols have been shown to inhibit the activation of AP-1, which often is ascribed to the anti-oxidant properties of these natural products.


METHODS
In the present study, a library of substituted trans-stilbenes, including polyphenols, was screened for activity against the TPA-induced activation of AP-1 using the Panomics AP-1 Reporter 293 Stable Cell Line, which is designed for screening potential inhibitors or activators.


RESULTS
Several trans-stilbenes were identified that inhibit TPA-induced activation of AP-1, with IC50 values as low as 0.5 microM. Moreover, some other trans-stilbenes were able to enhance the effects of TPA 2 to 3-fold. Many of the trans-stilbenes identified as inhibitors or enhancers are devoid of anti-oxidant properties.


CONCLUSIONS
The ability of trans-stilbenes to inhibit or enhance the effects of TPA does not depend upon their anti-oxidant properties.
Deck
Lorraine M
LM
Department of Chemistry, University of New Mexico, Albuquerque, NM 87131, USA. ldeck@unm.edu
Hunsaker
Lucy A
LA
Gonzales
Amanda M
AM
Orlando
Robert A
RA
Vander Jagt
David L
DL
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002460:Cell Line; D015232:Dinoprostone / Q000032:analysis / Q000494:pharmacology; D005419:Flavonoids; D006801:Humans; D051379:Mice; D010636:Phenols; D059808:Polyphenols; D000077185:Resveratrol; D013267:Stilbenes / Q000819:agonists / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
D000975:Antioxidants; D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D013267:Stilbenes; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate; D000077185:Resveratrol