Lactacystin inhibits cathepsin A activity in melanoma cell lines.

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.
AuthorsL Kozlowski, T Stoklosa, S Omura, C Wójcik, M Z Wojtukiewicz, K Worowski, H Ostrowska
JournalTumour 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] Switzerland
PMID11399945 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright 2001 S. Karger AG, Basel
Chemical References
  • Antibiotics, Antineoplastic
  • Cysteine Proteinase Inhibitors
  • Enzyme Inhibitors
  • Oligopeptides
  • benzyloxycarbonyl-isoleucyl-glutamyl(O-tert-butyl)-alanyl-leucinal
  • lactacystin
  • epoxomicin
  • Carboxypeptidases
  • Cathepsin A
  • Acetylcysteine
  • 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

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