Journal
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
Volume 57, Issue 1, Pages 76-82Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jf802881d
Keywords
Indole-3-carbinol; matrix metalloproteinase; Sp1; extracellular signal-regulated kinase
Ask authors/readers for more resources
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
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available