Inhibitory effect of the carnosine-gallic acid synthetic peptide on MMP-2 and MMP-9 in human fibrosarcoma HT1080 cells

J Pept Sci. 2014 Sep;20(9):716-24. doi: 10.1002/psc.2658. Epub 2014 Jun 23.

Abstract

Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that degrade extracellular matrix components and play important roles in a variety of biological and pathological processes such as malignant tumor metastasis and invasion. In this study, we constructed carnosine-gallic acid peptide (CGP) to identify a better MMP inhibitor than carnosine. The inhibitory effects of CGP on MMP-2 and MMP-9 were investigated in the human fibrosarcoma (HT1080) cell line. As a result, CGP significantly decreased MMP-2 and MMP-9 expression levels without a cytotoxic effect. Moreover, CGP may inhibit migration and invasion in HT1080 cells through the urokinase plasminogen activator (uPA)-uPA receptor signaling pathways to inhibit MMP-2 and MMP-9. Based on these results, it appears that CGP may play an important role in preventing and treating several MMP-2 and MMP-9-mediated health problems such as metastasis.

Keywords: HT1080 cell; carnosine-gallic acid peptide; matrix metalloproteinase-2 and -9; urokinase plasminogen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents* / chemical synthesis
  • Antineoplastic Agents* / chemistry
  • Carnosine / chemical synthesis
  • Carnosine / chemistry
  • Carnosine / pharmacology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Fibrosarcoma / drug therapy*
  • Fibrosarcoma / enzymology
  • Fibrosarcoma / pathology
  • Gallic Acid / chemical synthesis
  • Gallic Acid / chemistry
  • Gallic Acid / pharmacology
  • Humans
  • Matrix Metalloproteinase 2 / metabolism*
  • Matrix Metalloproteinase 9 / metabolism*
  • Matrix Metalloproteinase Inhibitors* / chemical synthesis
  • Matrix Metalloproteinase Inhibitors* / chemistry
  • Neoplasm Invasiveness
  • Peptides* / chemical synthesis
  • Peptides* / chemistry
  • Peptides* / pharmacology

Substances

  • Antineoplastic Agents
  • Matrix Metalloproteinase Inhibitors
  • Peptides
  • Gallic Acid
  • Carnosine
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9