α-Mangostin Suppresses PC-3 Human Prostate Carcinoma Cell Metastasis by Inhibiting Matrix Metalloproteinase-2/9 and Urokinase-Plasminogen Expression through the JNK Signaling Pathway

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• 作者：Shun-Hsing Hung^† ; ; Kun-Hung Shen^† ; ^‡ ; ^§ ; ; Cheng-Hsun Wu ; Chang-Liang Liu^† ; ; Yuan-Wei Shih*
• 刊名：Journal of Agricultural and Food Chemistry
• 出版年：2009
• 出版时间：February 25, 2009
• 年：2009
• 卷：57
• 期：4
• 页码：1291-1298
• 全文大小：456K
• 年卷期：v.57,no.4(February 25, 2009)
• ISSN：1520-5118

文摘

α-Mangostin, a component of Garcinia mangostana Linn, is a xanthone derivative shown to have antioxidant and anticarcinogen properties. In this study, we first report the antimetastatic effect of α-mangostin in the human prostate carcinoma cell line PC-3. The results show that α-mangostin exhibited an inhibitory effect on the abilities of adhesion, migration, and invasion by cell-matrix adhesion assay, wound healing assay, and Boyden chamber assay. In the cancer cell metastasis process, matrix degrading proteinases are required. Results from zymography showed that α-mangostin treatment could decrease the expressions of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and urokinase-plasminogen activator (u-PA) in a concentration-dependent manner. Moreover, α-mangostin also exerted an inhibitory effect on phosphorylation of c-Jun N-terminal kinase 1 and 2 (JNK1/2) and inhibition of activation of nuclear factor kappa B (NF-κB), c-Fos, and c-Jun. Furthermore, the treatment of inhibitors specific for JNK (SP600125) to PC-3 cells could result in a reduced expression of MMP-2, MMP-9, and u-PA. These results demonstrated that α-mangostin could mediate PC-3 cells metastasis by reduction of MMP-2, MMP-9, and u-PA expression through the suppression of the JNK1/2 signaling pathway and inhibition of NF-κB and AP-1 binding activity. These findings proved that α-mangostin might be offered further application as an antimetastatic agent.