Caffeoyl pyrrolidine derivative LY52 inhibits tumor invasion and metastasis via suppression of matrix metalloproteinase activity

Anticancer Res. 2006 Sep-Oct;26(5A):3573-8.

Abstract

Background: LY52 is a caffeoyl pyrrolidine derivative designed to fit and extend into the active pocket of matrix metalloproteinase (MMP). In this study, the effects of LY52 on MMP-2 and MMP-9 activities and tumor invasion and metastasis were examined.

Materials and methods: MMP expression in SKOV3 cells was analyzed by gelatin zymography. The anti-invasion and anti-metastasis abilities of LY52 were evaluated with penetration of SKOV3 cells through Matrigel-coated membrane in vitro and pulmonary metastasis of Lewis lung carcinoma in mice, respectively.

Results: LY52 significantly blocked the proteolytic activity of gelatinase. Gelatin zymography revealed that MMP-2 and MMP-9 expressions in SKOV3 cells were reduced in the presence of LY52. LY52 also suppressed SKOV3 cell invasion in vitro. Furthermore, a significant inhibition of pulmonary metastasis of Lewis lung carcinoma cells was observed in LY52-administrated mice.

Conclusion: LY52 might suppress invasion and metastasis of carcinoma cells via inhibition of MMP-2 and MMP-9 proteolytic activities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caffeic Acids / therapeutic use*
  • Carcinoma, Lewis Lung / enzymology
  • Carcinoma, Lewis Lung / prevention & control*
  • Carcinoma, Lewis Lung / secondary
  • Cell Proliferation / drug effects
  • Collagen / metabolism
  • Drug Combinations
  • Electrophoresis, Polyacrylamide Gel
  • Female
  • Laminin / metabolism
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / prevention & control
  • Lung Neoplasms / secondary
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Matrix Metalloproteinase Inhibitors*
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Invasiveness / prevention & control*
  • Ovarian Neoplasms / enzymology
  • Ovarian Neoplasms / prevention & control*
  • Ovarian Neoplasms / secondary
  • Proteoglycans / metabolism
  • Pyrrolidines / therapeutic use*
  • Tumor Cells, Cultured

Substances

  • Caffeic Acids
  • Drug Combinations
  • Laminin
  • Matrix Metalloproteinase Inhibitors
  • Proteoglycans
  • Pyrrolidines
  • matrigel
  • Collagen
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • pyrrolidine