N-(4-hydroxyphenyl)retinamide inhibits breast cancer cell invasion through suppressing NF-KB activation and inhibiting matrix metalloproteinase-9 expression

Riferimento: 
J Cell Biochem. 2012 Sep;113(9):2845-55.
Autori: 
Kang H, Lee M, Choi KC, Shin DM, Ko J, Jang SW.
Fonte: 
J Cell Biochem. 2012 Sep;113(9):2845-55.
Anno: 
2012
Azione: 
Il retinoide sintetico N-(4-idrossifenil) retinamide (4-HPR) inibisce l'invasione e l'espressione della metalloproteinasi (MMP) -9 nella linea cellulare del cancro mammario altamente metastatico.
Target: 
4-HPR/cancro mammario.

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.

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