title: Galangin and kaempferol suppress phorbol-12-myristate-13-acetate-induced matrix metalloproteinase-9 expression in human fibrosarcoma HT-1080 cells.
abstract: Matrix metalloproteinase (MMP)-9 degrades type IV collagen in the basement membrane and plays crucial roles in several pathological implications, including tumorigenesis and inflammation. In this study, we analyzed the effect of flavonols on MMP-9 expression in phorbol-12-myristate-13-acetate (PMA)-induced human fibrosarcoma HT-1080 cells. Galangin and kaempferol efficiently decreased MMP-9 secretion, whereas fisetin only weakly decreased its secretion. Galangin and kaempferol did not affect cell viability at concentrations up to 30 μM. Luciferase reporter assays showed that galangin and kaempferol decrease transcription of MMP-9 mRNA. Moreover, galangin and kaempferol strongly reduce IκBα phosphorylation and significantly decrease JNK phosphorylation. These results indicate that galangin and kaempferol suppress PMA-induced MMP-9 expression by blocking activation of NF-κB and AP-1. Therefore, these flavonols could be used as chemopreventive agents to lower the risk of diseases involving MMP-9.
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea.
authors.forename: Yu Jung
authors.initials: YJ
authors.lastname: Choi
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea.
authors.forename: Young Hun
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea.
authors.forename: Seung-Taek
authors.initials: ST
authors.lastname: Lee
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005354:Fibrosarcoma / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D044949:Kaempferols / Q000494:pharmacology*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives* / Q000633:toxicity
chemical_list: D005419:Flavonoids; D020672:I-kappa B Proteins; D044949:Kaempferols; C000606204:NFKBIA protein, human; D000072000:NF-KappaB Inhibitor alpha; C037032:galangin; C016658:phorbolol myristate acetate; C006552:kaempferol; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D013755:Tetradecanoylphorbol Acetate
keywords: MMP-9; NF-κB; flavonol; galangin; kaempferol; mitogen-activated protein kinase