α‐Mangostin, A Novel Dietary Xanthone, Suppresses TPA‐Mediated MMP‐2 and MMP‐9 Expressions through the ERK Signaling Pathway in MCF‐7 Human Breast Adenocarcinoma Cells

Abstract

This study first investigates the anti‐metastatic effect of α‐mangostin on 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA)‐induced matrix metalloproteinase‐2 (MMP‐2) and matrix metalloproteinase‐9 (MMP‐9) expressions in human breast adenocarcinoma cells, MCF‐7. First, the result demonstrated α‐mangostin could inhibit TPA‐induced abilities of the adhesion, invasion, and migration by cell‐matrix adhesion assay and Boyden chamber assay. Data also showed α‐mangostin could inhibit the activation of extracellular signal‐regulated kinase 1 and 2 (ERK1/2) involved in the downregulation the enzyme activities, protein, and messenger RNA levels of MMP‐2 and MMP‐9 induced by TPA. Next, α‐mangostin also strongly inhibited TPA‐induced degradation of inhibitor of kappaBα (IκBα) and the nuclear levels of nuclear factor kappa B (NF‐κB), c‐Fos, and c‐Jun. Also, a dose‐dependent inhibition on the binding abilities of NF‐κB and activator protein‐1 (AP‐1) by α‐mangostin treatment was further observed. Further, the treatment of specific inhibitor for ERK (U0126) to MCF‐7 cells could inhibit TPA‐induced MMP‐2 and MMP‐9 expressions along with an inhibition on cell invasion and migration. Presented data reveal that α‐mangostin is a novel, effective, antimetastatic agent that functions by downregulating MMP‐2 and MMP‐9 gene expressions.