alpha-Mangostin Suppresses Phorbol 12-myristate 13-acetate-Induced MMP-2/MMP-9 Expressions via alpha v beta 3 Integrin/FAK/ERK and NF-kappa B Signaling Pathway in Human Lung Adenocarcinoma A549 Cells

作者：Shih Yuan Wei; Chien Shang Tao; Chen Pin Shern; Lee Jian Hui; Wu Shu Hau; Yin Li Te^*

来源：Cell Biochemistry and Biophysics, 2010, 58(1): 31-44.

DOI：10.1007/s12013-010-9091-2

• alpha-Mangostin
• PMA
• Invasion
• Migration
• alpha v beta 3 Integrin
• FAK
• ERK1/2
• MMP-2
• MMP-9

The purpose of this study is to investigate the anti-metastatic effect of alpha-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, alpha-mangostin could inhibit PMA-induced abilities of the adhesion, invasion, and migration. Data also showed alpha-mangostin could inhibit the activation of alpha v beta 3 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, alpha-mangostin also strongly inhibited PMA-induced degradation of inhibitor of kappaB alpha (I kappa B alpha) and the nuclear levels of nuclear factor kappa B (NF-kappa B). Also, a dose-dependent inhibition on the binding abilities of NF-kappa B by alpha-mangostin treatment was further observed. Furthermore, reduction of FAK or ERK1/2 phosphorylation by FAK small interfering RNA (FAK siRNA) potentiated the effect of alpha-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 alpha-mangostin is a novel, effect, anti-metastatic agent that functions by downregulating MMP-2 and MMP-9 gene expressions.

• 出版日期2010-9