RESUMEN
This study first investigates the anti-metastatic effect of alpha-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 alpha-mangostin could inhibit TPA-induced abilities of the adhesion, invasion, and migration by cell-matrix adhesion assay and Boyden chamber assay. Data also showed alpha-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, alpha-mangostin also strongly inhibited TPA-induced degradation of inhibitor of kappaBalpha (IkappaBalpha) and the nuclear levels of nuclear factor kappa B (NF-kappaB), c-Fos, and c-Jun. Also, a dose-dependent inhibition on the binding abilities of NF-kappaB and activator protein-1 (AP-1) by alpha-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 alpha-mangostin is a novel, effective, antimetastatic agent that functions by downregulating MMP-2 and MMP-9 gene expressions.
Asunto(s)
Adenocarcinoma/enzimología , Neoplasias de la Mama/enzimología , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/genética , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Acetato de Tetradecanoilforbol/farmacología , Xantonas/farmacología , Adenocarcinoma/patología , Western Blotting , Neoplasias de la Mama/patología , Carcinógenos/antagonistas & inhibidores , Carcinógenos/farmacología , Adhesión Celular/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , ADN de Neoplasias/genética , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Inhibidores de Proteínas Quinasas/farmacología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Acetato de Tetradecanoilforbol/antagonistas & inhibidores , Cicatrización de Heridas/efectos de los fármacosRESUMEN
This study first investigates the anti-metastatic effect of plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MMPs and u-PA expressions in human lung cancer cells, A549. First, the result demonstrated plumbagin could inhibit TPA induced the abilities of the adhesion, invasion, and migration by cell-matrix adhesion assay and Boyden chamber assay. Data also showed plumbagin could inhibit the activation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) involved in the down-regulating enzyme activities, protein and messenger RNA levels of matrix metalloproteinase-2 (MMP-2), and urokinase-type plasminogen activator (u-PA) induced by TPA. Next, plumbagin also strongly inhibited TPA-induced phosphorylation and degradation of inhibitor of kappaBalpha (IkappaBalpha), and the nuclear levels of nuclear factor kappa B (NF-kappaB), c-Fos, and c-Jun. Also, a dose-dependent inhibition on the binding abilities of NF-kappaB and activator protein-1 (AP-1) by plumbagin treatment was further observed. Further, the treatment of specific inhibitor for ERK (U0126) to A549 cells could inhibit TPA-induced MMP-2 and u-PA expressions along with an inhibition on cell invasion and migration. Presented data reveals that plumbagin is a novel, effective, anti-metastatic agent that functions by down-regulating MMP-2 and u-PA gene expressions.
