title: N-(4-hydroxyphenyl)retinamide inhibits breast cancer cell invasion through suppressing NF-KB activation and inhibiting matrix metalloproteinase-9 expression.
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.
authors.affiliation: Department of Medicine, Graduate School, University of Ulsan, Pungnap-2 dong, Songpa-gu, Seoul, South Korea.
authors.forename: Hyereen
authors.initials: H
authors.lastname: Kang
authors.forename: Minjae
authors.initials: M
authors.lastname: Lee
authors.forename: Kyung-Chul
authors.initials: KC
authors.lastname: Choi
authors.forename: Dong-Myoung
authors.initials: DM
authors.lastname: Shin
authors.forename: Jesang
authors.initials: J
authors.lastname: Ko
authors.forename: Sung-Wuk
authors.initials: SW
authors.lastname: Jang
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D017313:Fenretinide / Q000494:pharmacology*; D006801:Humans; D015151:Immunoblotting; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D016328:NF-kappa B; D017313:Fenretinide; D020780:Matrix Metalloproteinase 9; D013755:Tetradecanoylphorbol Acetate