Indole-3-carbinol inhibits Sp1-induced matrix metalloproteinase-2 expression to attenuate migration and invasion of breast cancer cells.
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.
Hung
Wen-Chun
WC
Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.
Chang
Hui-Chiu
HC
D001665:Binding Sites / Q000235:genetics; D019607:Brassicaceae / Q000737:chemistry; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction; D016329:Sp1 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*
D007211:Indoles; D012333:RNA, Messenger; D016329:Sp1 Transcription Factor; C016517:indole-3-carbinol; D048049:Extracellular Signal-Regulated MAP Kinases; D020778:Matrix Metalloproteinase 2