Effect of cysteine proteinase inhibitors on murine B16 melanoma cell invasion in vitro

Biol Chem. 2002 May;383(5):839-42. doi: 10.1515/BC.2002.088.

Abstract

Various types of proteinases are implicated in the malignant progression of human and animal tumors. Proteinase inhibitors may therefore be useful as therapeutic agents in anti-invasive and anti-metastatic treatment. The aims of this study were (1) to estimate the relative importance of proteinases in B16 cell invasion in vitro using synthetic, class-specific proteinase inhibitors and (2) to assess the inhibitory effect of some naturally occurring cysteine proteinase inhibitors. Serine proteinase inhibitor reduced invasiveness by up to 24%, whereas inhibition of aspartic proteinases reduced invasion by 11%. Synthetic inhibitors of cysteine proteinases markedly impaired invasion: cathepsin B inhibitors, particularly Ca-074Me, inhibited invasion from 20-40%, whereas cathepsin L inhibitor Clik 148 reduced invasion by 11%. The potato cysteine proteinase inhibitor PCPI 8.7 inhibited invasion by 21%, whereas another potato inhibitor, PCPI 6.6, and the mushroom cysteine proteinase inhibitor clitocypin had no effects. As the inhibitors that inhibited cathepsin B were in general more efficient at impairing the invasiveness, we conclude that of the two cysteine proteinases, cathepsin B plays a more important role than cathepsin L in murine melanoma cell invasion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cathepsin B / antagonists & inhibitors*
  • Cathepsin L
  • Cathepsins / antagonists & inhibitors*
  • Cysteine Endopeptidases
  • Cysteine Proteinase Inhibitors / pharmacology*
  • Fungal Proteins / pharmacology
  • Kinetics
  • Melanoma, Experimental / drug therapy
  • Melanoma, Experimental / enzymology*
  • Melanoma, Experimental / pathology
  • Neoplasm Invasiveness
  • Solanum tuberosum / enzymology
  • Tumor Cells, Cultured

Substances

  • Clitocypin protein, Clitocybe nebularis
  • Cysteine Proteinase Inhibitors
  • Fungal Proteins
  • Cathepsins
  • Cysteine Endopeptidases
  • Cathepsin B
  • CTSL protein, human
  • Cathepsin L