Document Detail


Indole-3-carbinol inhibits Sp1-induced matrix metalloproteinase-2 expression to attenuate migration and invasion of breast cancer cells.
MedLine Citation:
PMID:  19061309     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Indole-3-carbinol (I3C), a major indole metabolite in cruciferous vegetables, has been shown to inhibit invasion of breast cancer cells. This study addressed the effect of I3C on the expression of matrix metalloproteinases (MMPs) and clarified the underlying mechanism. Migration, invasion, and MMP-2 activity of MCF-7 breast cancer cells were dose-dependently inhibited by I3C. In addition, the MMP-2 mRNA level was also reduced by I3C. Promoter deletion and mutation analysis suggested that I3C inhibited MMP-2 gene transcription via the -85/-7 bp promoter region and the Sp1 transcription factor binding site located within the -72/-64 bp promoter region was important for the inhibition. Chromatin immunoprecipitation assay confirmed that Sp1 proteins constitutively bound to this consensus sequence in vivo and that the binding was attenuated by I3C. In addition, I3C inhibited the extracellular signal-regulated kinase (ERK) signaling pathway in MCF-7 cells. The results suggest that I3C inhibits MMP-2 expression by blocking the ERK/Sp1-mediated gene transcription to attenuate migration and invasion of breast cancer cells.
Authors:
Wen-Chun Hung; Hui-Chiu Chang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of agricultural and food chemistry     Volume:  57     ISSN:  1520-5118     ISO Abbreviation:  J. Agric. Food Chem.     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2009-01-07     Completed Date:  2009-02-13     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0374755     Medline TA:  J Agric Food Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  76-82     Citation Subset:  IM    
Affiliation:
Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.
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MeSH Terms
Descriptor/Qualifier:
Binding Sites / genetics
Brassicaceae / chemistry
Breast Neoplasms
Cell Line, Tumor
Cell Movement / drug effects
Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
Gene Expression / drug effects*
Humans
Indoles / pharmacology*
Matrix Metalloproteinase 2 / genetics*,  metabolism
Neoplasm Invasiveness / prevention & control*
Promoter Regions, Genetic / genetics
RNA, Messenger / analysis
Signal Transduction
Sp1 Transcription Factor / antagonists & inhibitors,  metabolism,  pharmacology*
Chemical
Reg. No./Substance:
0/Indoles; 0/RNA, Messenger; 0/Sp1 Transcription Factor; 700-06-1/indole-3-carbinol; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases; EC 3.4.24.24/Matrix Metalloproteinase 2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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