Lactacystin inhibits cathepsin A activity in melanoma cell lines

Leszek Kozłowski, Tomasz Stokłosa, Satoshi Omura, Cezary Wójcik, Marek Z. Wojtukiewicz, Krzysztof Worowski, Halina Ostrowska

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

We describe the inhibitory effect of the proteasome inhibitor, lactacystin, on cathepsin A activity in murine melanoma cell lines. In vitro lactacystin metabolite, β-lactone, at a concentration of 1 μM, 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 μM 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 μM 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.

Original languageEnglish (US)
Pages (from-to)211-215
Number of pages5
JournalTumor Biology
Volume22
Issue number4
DOIs
StatePublished - Jul 9 2001

Keywords

  • Cathepsin A
  • Lactacystin
  • Melanoma cell lines

ASJC Scopus subject areas

  • Cancer Research

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  • Cite this

    Kozłowski, L., Stokłosa, T., Omura, S., Wójcik, C., Wojtukiewicz, M. Z., Worowski, K., & Ostrowska, H. (2001). Lactacystin inhibits cathepsin A activity in melanoma cell lines. Tumor Biology, 22(4), 211-215. https://doi.org/10.1159/000050618