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

Chem Biol Interact. 2009 Sep 14;181(1):8-14. doi: 10.1016/j.cbi.2009.05.009. Epub 2009 May 21.

Abstract

Penta-acetyl geniposide [(Ac)(5)GP], an acetylated geniposide product from Gardenia fructus, has been known to have hepatoprotective 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)(5)GP 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)(5)GP treatment. Further (Ac)(5)GP also exerted an inhibitory effect on phosphoinositide 3-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-kappaB), c-Fos, c-Jun. These findings proved (Ac)(5)GP is highly likely to be a inhibiting cancer migration agent to be further developed in the future.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line, Tumor
  • DNA Primers
  • Electrophoresis, Polyacrylamide Gel
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Glioma / pathology*
  • Glucosides / pharmacology*
  • Iridoid Glucosides
  • Iridoids / pharmacology*
  • Matrix Metalloproteinase Inhibitors*
  • Neoplasm Metastasis / prevention & control*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Protease Inhibitors / pharmacology*
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects*

Substances

  • DNA Primers
  • Glucosides
  • Iridoid Glucosides
  • Iridoids
  • Matrix Metalloproteinase Inhibitors
  • Protease Inhibitors
  • pentaacetyl geniposide
  • Phosphatidylinositol 3-Kinases
  • Extracellular Signal-Regulated MAP Kinases