Inhibitory effect of penta-acetyl geniposide on C6 glioma cells metastasis by inhibiting matrix metalloproteinase-2 expression involved in both the PI3K and ERK signaling pathways

Penta-acetyl geniposide [(Ac)(5)GP]. an acetylated geniposide product from Gardenia fructus, has been known to have hepato protective properties and recent studies have revealed its anti-proliferative and apoptotic effect on C6 glioma cells. In this study, we first report the anti-metastastic effect of (Ac)(5)GP in the rat neuroblastoma line: C6 glioma cells. First (Ac)5GP exhibited an inhibitory effect on abilities of adhesion and motility by cell-matrix adhesion assay, wound healing assay and Boyden chamber assay. Second, the decreasing activity of matrix metalloproteinase-2 (MMP-2) was noted by gelatin zymography assay. Further analysis with semi-quantitative RT-PCR showed the mRNA levels of MMP-2 and membrane type I matrix metalloproteinase (MT1-MMP) were significantly reduced, while the tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) was elevated by (Ac)5GP treatment. Further (Ac)5GP also exerted an inhibitory effect on phosphoinositide3-kinase (PI3K) protein expression. phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and inhibition of activation of transcription factor nuclear factor kappa B (NF-kappa B). c-Fos, c-Jun. These findings proved (Ac)5GP is highly likely to be a inhibiting cancer migration agent to be further developed in the future. Crown Copyright (C) 2009 Published by Elsevier Ireland Ltd. All rights reserved.