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

Pei-Chien Tsai, Chiao-Lun Chu, Chih-Hua Tseng, Yeh-Long Chen, Long-Sen Chang, Shinne-Ren Lin
Clinical and Experimental Pharmacology & Physiology 2014, 41 (9): 716-26
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.

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