The purpose of this study is to investigate the anti-metastatic effect of α-mangostin on phorbol 12-myristate 13-acetate (PMA)-induced matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) expressions in A549 human lung adenocarcinoma cells. Firstly, α-mangostin could inhibit PMA-induced abilities of the adhesion, invasion, and migration. Data also showed α-mangostin could inhibit the activation of αvβ3 integrin, focal adhesion kinase (FAK), and extracellular signal-regulated kinase1/2 (ERK1/2) involved in the downregulation the enzyme activities, protein and messenger RNA levels of MMP-2 and MMP-9 induced by PMA. Next, α-mangostin also strongly inhibited PMA-induced degradation of inhibitor of kappaBα (IκBα) and the nuclear levels of nuclear factor kappa B (NF-κB). Also, a dose-dependent inhibition on the binding abilities of NF-κB by α-mangostin treatment was further observed. Furthermore, reduction of FAK or ERK1/2 phosphorylation by FAK small interfering RNA (FAK siRNA) potentiated the effect of α-mangostin. Finally, the transient transfection of ERK siRNA significantly down-regulated the expressions of MMP-2 and MMP-9 concomitantly with a marked inhibition on cell invasion and migration. Presented results indicated α-mangostin is a novel, effect, anti-metastatic agent that functions by downregulating MMP-2 and MMP-9 gene expressions.
