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

作者：Hung Shun Hsing; Shen Kun Hung; Wu Cheng Hsun; Liu Chang Liang; Shih Yuan Wei

来源：Journal of Agricultural and Food Chemistry, 2009, 57(4): 1291-1298.

DOI：10.1021/jf8032683

• alpha-Mangostln
• metastasis
• MMP-2
• MMP-9
• u-PA
• NF-kappa B
• AP-1

alpha-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 a-mangostin in the human prostate carcinoma cell line PC-3. The results show that alpha-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 alpha-mangostin treatment could decrease the expressions of matrix metal loproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and urokinase-plasminogen activator (u-PA) in a concentration-dependent manner. Moreover, alpha-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-kappa B), 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 alpha-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-kappa B and AP-1 binding activity. These findings proved that alpha-mangostin might be offered further application as an antimetastatic agent.

• 出版日期2009-2-25
• 单位中国医科大学