Naphtho[1,2-b]furan-4,5-dione inhibits MDA-MB-231 cell migration and invasion by suppressing Src-mediated signaling pathways.

ABSTRACT

Naphtho[1,2-b]furan-4,5-dione (NFD), a bioactive component of Avicennia marina, has been demonstrated to display anti-cancer activity. Breast cancer is a highly malignant carcinoma and most deaths of breast cancer are caused by metastasis. In this study, we showed that NFD blocked migration and invasion of MDA-MB-231 breast cancer cells without affecting apoptosis or growth arrest. NFD caused significant block of Src kinase activity in MDA-MB-231 cells. Moreover, NFD treatment was correlated with reduced phosphorylation of FAK at Tyr 576/577, 861 and 925 sites, p130(Cas) at Tyr 410, and paxillin at Tyr 118. NFD also suppressed the activation of phosphatidylinositol 3-kinase/Akt. Consistent with inhibition of these signaling pathways and invasion, NFD reduced the expression of matrix metalloproteinase-9. Furthermore, Src antagonist PP2 caused a significant decrease in the phosphorylation of FAK, p130(Cas), paxillin, and PI3K/Akt. Our findings provide evidences that NFD inhibits Src-mediated signaling pathways involved in controlling breast cancer migration and invasion, suggesting that it has a therapeutic potential in breast cancer treatment.