Inhibitory effects of GL-V9 on the invasion of human breast carcinoma cells by downregulating the expression and activity of matrix metalloproteinase-2/9

Eur J Pharm Sci. 2011 Aug 17;43(5):393-9. doi: 10.1016/j.ejps.2011.06.001. Epub 2011 Jun 13.

Abstract

Cancer cell invasion plays a crucial role in growth and local spreading of tumors. GL-V9 is a newly synthesized flavonoid that has been shown to possess an antitumor effect. However, the mechanism of GL-V9 in preventing tumor growth is still unclear. The purpose of this study is to investigate the anti-invasive and anti-metastatic activity of this novel compound in MDA-MB-231 and MCF-7 human breast carcinoma cells. In this study, GL-V9 caused a concentration-dependent suppression of cell adhesive ability by cell adhesion assay, it also inhibited the migration and invasion of cells by wound healing assay and transwell invasion assay in a concentration-dependent manner. Considering matrix metalloproteinases (MMPs) play an important role in metastatic process, we used western blotting and gelatin zymography to examine the effect of GL-V9 on the expression and activity of MMPs. The mechanism revealed that GL-V9 significantly suppressed the expression and activity of MMP-2 and MMP-9. Furthermore, GL-V9 suppressed their upstream protein kinases activation by reducing phosphorylated forms of serine/threonine kinase AKT and c-Jun N-terminal kinase. These findings suggested that GL-V9 could inhibit the invasion of tumor cells by downregulating the expression and activity of MMP-2 and MMP-9, potentially associating with the suppression of phosphorylation of AKT and JNK.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / pathology*
  • Cell Adhesion / drug effects
  • Cell Line, Tumor
  • Down-Regulation / drug effects*
  • Female
  • Flavonoids / pharmacology*
  • Humans
  • Matrix Metalloproteinase 2 / metabolism*
  • Matrix Metalloproteinase 9 / metabolism*
  • Neoplasm Invasiveness / prevention & control*
  • Phosphorylation

Substances

  • 5-hydroxy-8-methoxy-2-phenyl-7-(4-(pyrrolidin-1-yl)butoxy)4H-chromen-4-one
  • Flavonoids
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9