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

Hyereen Kang, Minjae Lee, Kyung Chul Choi, Dong Myoung Shin, Jesang Ko, Sung Wuk Jang

Research output: Contribution to journalArticle

30 Citations (Scopus)

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 languageEnglish
Pages (from-to)2845-2855
Number of pages11
JournalJournal of cellular biochemistry
Volume113
Issue number9
DOIs
Publication statusPublished - 2012 Sep

Keywords

  • 4-HPR
  • MMP-9
  • NF-κB
  • breast cancer
  • cell invasion

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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