title: Inhibitory action of naphtho[1,2-b]furan-4,5-dione on hepatocyte growth factor-induced migration and invasion of MDA-MB-231 cells: mechanisms of action.
abstract: Naphtho[1,2-b]furan-4,5-dione (NFD), a bioactive component of Avicennia marina, has been shown to exhibit anticancer activity. The aim of the present study was to explore the effect of NFD on hepatocyte growth factor (HGF)-induced cell migration and invasion of MDA-MB-231 human breast cancer cells, as well as the underlying mechanism of action. Cell viability was determined using the 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide assay, western blot analysis was used to measure protein expression and cell migration and invasion were evaluated by the cell wound healing assay, Boyden chamber assay and gelatin zymography. When cells were treated with non-toxic concentrations of NFD (1-3 μmol/L, 24 h), NFD concentration-dependently inhibited HGF-promoted cell migration and invasion. Simultaneously, NFD efficiently suppressed c-Met phosphorylation and downstream activation of phosphatidylinositol 3-kinase (PI3K) and Akt. In addition, NFD inhibited the phosphorylation of IκB kinases and IκBα and nuclear translocation of nuclear factor (NF)-κB, as well as matrix metalloproteinase (MMP)-9 activity. Furthermore, the c-Met inhibitor PHA665752 (10 μmol/L) inhibited HGF-induced MMP-9 expression, cell migration and invasion, as well as the activation of PI3K/Akt, suggesting that PI3K/Akt activation occur downstream of c-Met activation. In conclusion, the results of the present study suggest that NFD inhibits HGF-induced invasion and migration of MDA-MB-231 cells via HGF- and/or c-Met-mediated PI3K/Akt and NF-κB signalling pathways, leading to downregulation of MMP-9 expression and cell migration.
authors.affiliation: Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Pei-Chien
authors.initials: PC
authors.lastname: Tsai
authors.forename: Chiao-Lun
authors.initials: CL
authors.lastname: Chu
authors.forename: Chih-Hua
authors.initials: CH
authors.lastname: Tseng
authors.forename: Yeh-Long
authors.initials: YL
authors.lastname: Chen
authors.forename: Long-Sen
authors.initials: LS
authors.lastname: Chang
authors.forename: Shinne-Ren
authors.initials: SR
authors.lastname: Lin
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D017228:Hepatocyte Growth Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009285:Naphthoquinones / Q000494:pharmacology*; D009361:Neoplasm Invasiveness / Q000473:pathology*; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013450:Sulfones / Q000494:pharmacology
chemical_list: C480541:5-((2,6-dichlorobenzyl)sulfonyl)-3-((3,5-dimethyl-4-((2-(pyrrolidin-1-ylmethyl)pyrrolidin-1-yl)carbonyl)-1H-pyrrol-2-yl)methylene)-1,3-dihydro-2H-indol-2-one; D000970:Antineoplastic Agents; D007211:Indoles; D016328:NF-kappa B; D009285:Naphthoquinones; D013450:Sulfones; C073873:naphtho(1,2-b)furan-4,5-dione; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D020780:Matrix Metalloproteinase 9
keywords: MDA-MB-231 cell; c-Met signalling; hepatocyte growth factor; naphtho[1,2-b]furan-4,5-dione