Lactacystin inhibits cathepsin A activity in melanoma cell lines.

Abstract

We describe the inhibitory effect of the proteasome inhibitor, lactacystin, on cathepsin A activity in murine melanoma cell lines. In vitro lactacystin metabolite, beta-lactone, at a concentration of 1 microM, significantly suppressed cathepsin A activity in B78 melanoma cell lysates by about 50%. Exposure of three murine melanoma cell lines with different metastatic potential to lactacystin at a concentration of 5 microM for 6 h caused a significant reduction in the carboxypeptidase activity of this enzyme, while the inhibitory activity remained unchanged for at least 12 h. Other proteasome-specific inhibitors, e.g. epoxomicin and N-benzyloxycarbonyl-Ile-Glu(O-tert-Bu)-Ala-leucinal (PSI) at a concentration of 1 microM did not affect cathepsin A activity in melanoma cell line lysates. These data support our previous proposal that lactacystin is not a specific inhibitor of the proteasome. Since cathepsin A is also a tumor-associated enzyme, further research is needed to clarify its role and the significance of its inhibition by lactacystin in tumor biology.

• Authors: L Kozlowski, T Stoklosa, S Omura, C Wójcik, M Z Wojtukiewicz, K Worowski, H Ostrowska
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) 2001 Jul-Aug Vol. 22 Issue 4 Pg. 211-5 ISSN: 1010-4283 [Print] Netherlands
• PMID: 11399945 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2001 S. Karger AG, Basel

Chemical References

• Antibiotics, Antineoplastic
• Cysteine Proteinase Inhibitors
• Enzyme Inhibitors
• Oligopeptides
• benzyloxycarbonyl-isoleucyl-glutamyl(O-tert-butyl)-alanyl-leucinal
• lactacystin
• Carboxypeptidases
• Cathepsin A
• Acetylcysteine
• epoxomicin

Topics

• Acetylcysteine (analogs & derivatives, pharmacology)
• Animals
• Antibiotics, Antineoplastic (pharmacology)
• Carboxypeptidases (antagonists & inhibitors)
• Cathepsin A
• Cysteine Proteinase Inhibitors (pharmacology)
• Enzyme Inhibitors (pharmacology)
• Melanoma, Experimental (enzymology)
• Mice
• Oligopeptides (pharmacology)
• Tumor Cells, Cultured