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 |
|---|---|
| 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 1 |
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Keywords
- 4-HPR
- breast cancer
- cell invasion
- MMP-9
- NF-κB
ASJC Scopus subject areas
- Biochemistry
- Cell Biology
- Molecular Biology
Cite this
N-(4-hydroxyphenyl)retinamide inhibits breast cancer cell invasion through suppressing NF-KB activation and inhibiting matrix metalloproteinase-9 expression. / Kang, Hyereen; Lee, Minjae; Choi, Kyung Chul; Shin, Dong Myoung; Ko, Je Sang; Jang, Sung Wuk.
In: Journal of Cellular Biochemistry, Vol. 113, No. 9, 01.09.2012, p. 2845-2855.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - N-(4-hydroxyphenyl)retinamide inhibits breast cancer cell invasion through suppressing NF-KB activation and inhibiting matrix metalloproteinase-9 expression
AU - Kang, Hyereen
AU - Lee, Minjae
AU - Choi, Kyung Chul
AU - Shin, Dong Myoung
AU - Ko, Je Sang
AU - Jang, Sung Wuk
PY - 2012/9/1
Y1 - 2012/9/1
N2 - 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.
AB - 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.
KW - 4-HPR
KW - breast cancer
KW - cell invasion
KW - MMP-9
KW - NF-κB
UR - http://www.scopus.com/inward/record.url?scp=84863643540&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84863643540&partnerID=8YFLogxK
U2 - 10.1002/jcb.24159
DO - 10.1002/jcb.24159
M3 - Article
C2 - 22488409
AN - SCOPUS:84863643540
VL - 113
SP - 2845
EP - 2855
JO - Journal of Cellular Biochemistry
JF - Journal of Cellular Biochemistry
SN - 0730-2312
IS - 9
ER -