Abstract
Synthetic retinoid N-(4-hydroxyphenyl)retinamide (4-HPR) has been reported to exhibit anti-invasive and anti-metastatic activities by suppressing the enzymatic activity of matrix metalloproteinase (MMP)-9, but the underlying mechanism remains unclear. Here, we show that 4-HPR blocks the activity of MMP-9 in two ways: by reducing phorbol 12-myristate 13-acetate (PMA)-induced MMP-9 secretion and by suppressing cell invasion through the downregulation of MMP-9 gene transcription in MCF-7 breast cancer cells. 4-HPR inhibits the transcriptional activity of MMP-9 by reducing the DNA-binding activity of NF-κB on the MMP-9 promoter as well as by inhibiting the degradation of IκBα, leading to cytoplasmic accumulation of NF-κB. We also found that 4-HPR inhibits invasion and MMP-9 expression in the highly metastatic breast cancer cell line MDA-MB-231. Thus, 4-HPR might be a potent anti-invasive agent that works by suppressing MMP-9 expression via the NF-κB signaling pathway.
Original language | English |
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Pages (from-to) | 2845-2855 |
Number of pages | 11 |
Journal | Journal of cellular biochemistry |
Volume | 113 |
Issue number | 9 |
DOIs | |
Publication status | Published - 2012 Sep |
Keywords
- 4-HPR
- MMP-9
- NF-κB
- breast cancer
- cell invasion
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology