Document Detail


Nordihydroguaiaretic acid-mediated inhibition of ultraviolet B-induced activator protein-1 activation in human keratinocytes.
MedLine Citation:
PMID:  12112316     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Nordihydroguaiaretic acid (NDGA) is a polyphenolic compound from the Larrea tridentata bush that has been identified as a chemopreventive drug in animal studies. Topically applied NDGA has been shown to prevent phorbol ester promotion of tumors in mouse skin, suggesting that NDGA may be a candidate drug for the chemoprevention of skin cancer. Ultraviolet (UV) B irradiation from sunlight exposure is the major cause of human skin cancer. UVB irradiation causes epigenetic alterations in target keratinocytes, such as the upregulation of signal transduction pathways that induce the expression of transcription factors. Specifically, UVB induces activator protein-1 (AP-1), a transcription factor complex that alters normal cellular gene expression. A component of the UVB-induced AP-1 complex, c-fos, also was identified as a mediator of the signaling pathway that leads to AP-1 activation. Thus, NDGA was investigated as a potential inhibitory agent for UVB-induced signaling pathways in the human keratinocyte cell line HaCaT. NDGA significantly inhibited UVB-induced c-fos and AP-1 transactivation. In addition, NDGA was found to inhibit activity of phosphatidylinositol 3-kinase (PI 3-kinase), a UVB-inducible enzyme that contributes to the induced expression of c-fos and AP-1. Therefore, NDGA prevents UVB-induced c-fos expression and AP-1 transactivation by inhibiting the PI 3-kinase signaling pathway. Effective skin chemoprevention strategies may incorporate NDGA to inhibit components of the UVB-induced cell signaling pathways that increase AP-1 activity.
Authors:
Melissa Gonzales; G Tim Bowden
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Molecular carcinogenesis     Volume:  34     ISSN:  0899-1987     ISO Abbreviation:  Mol. Carcinog.     Publication Date:  2002 Jun 
Date Detail:
Created Date:  2002-07-11     Completed Date:  2002-07-31     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8811105     Medline TA:  Mol Carcinog     Country:  United States    
Other Details:
Languages:  eng     Pagination:  102-11     Citation Subset:  IM    
Copyright Information:
Copyright 2002 Wiley-Liss, Inc.
Affiliation:
Department of Molecular and Cellular Biology, Arizona Cancer Center, College of Medicine, University of Arizona, Tucson, USA.
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MeSH Terms
Descriptor/Qualifier:
Base Sequence
DNA / metabolism
Genes, fos
Humans
Keratinocytes / drug effects*,  metabolism,  radiation effects
Nordihydroguaiaretic Acid / pharmacology*
Phosphorylation
Transcription Factor AP-1 / antagonists & inhibitors*,  biosynthesis,  radiation effects
Transcription, Genetic / drug effects
Ultraviolet Rays*
Grant Support
ID/Acronym/Agency:
CA 27502/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Transcription Factor AP-1; 500-38-9/Nordihydroguaiaretic Acid; 9007-49-2/DNA

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