Peace and Safety

Another Consultation with the Muse of  Wellness.

Metalloproteinases:Enzymatic impact on cardiovascular and prostate health.

Metalloproteinase:Enzymatic impact on cardiovascular system.

An enzyme called matrix metalloproteinase-8 plays a crucial role in raising blood pressure and causing abnormal build-up of cells in the arteries – both of which increase the risk of heart disease.

The same metalloproteinase family of enzymes  is inhibited by alpha-mangostin found in the mangosteen fruit and impacts prostate cancer cells in the laboratory.

J Agric Food Chem. 2009 Feb 25;57(4):1291-8.

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.

Division of Urology, Department of Surgery, Chi Mei Medical Center, No. 901, Jhong-Hua Road, Yong-Kang, Tainan 710, Taiwan, Republic of China.

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 alpha-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 metalloproteinase-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-kappaB), 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-kappaB and AP-1 binding activity. These findings proved that alpha-mangostin might be offered further application as an antimetastatic agent.

James Tad Geiger MD