title: Apoptosis induced in L1210 leukaemia cells by an inhibitor of the chymotrypsin-like activity of the proteasome.
abstract: Of a number of factors involved in apoptosis, protease activity may play a crucial role. We show that N-benzyloxycarbonyl-Ile-Glu( O-t-butyl)-Ala-leucinal (PSI), a selective inhibitor of the chymotrypsin-like activity of the proteasome, induces massive apoptosis in murine leukaemia L1210 cells. At 50 nM concentration, PSI induces a block of cytokinesis, while higher concentrations (500 nM) cause S phase block and massive apoptosis. Z-Leu-leucinal, a specific calpain inhibitor, did not induce apoptosis. In contrast to previous reports, TNF-alpha did not enhance apoptosis when combined with PSI. Our results suggest that proteasome inhibitors may be considered as potential anti-neoplastic agents.
authors.affiliation: Laboratory for Molecular Cell Biology, Department of Histology and Embryology, Institute of Biostructure, Warsaw Medical School, Poland. cwojcik@ib.amwaw.edu.pl
authors.forename: C
authors.initials: C
authors.lastname: Wójcik
authors.forename: T
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authors.lastname: Stoklosa
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authors.lastname: Giermasz
authors.forename: J
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authors.lastname: Golab
authors.forename: R
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authors.lastname: Zagozdzon
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authors.lastname: Kawiak
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authors.lastname: Wilk
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authors.lastname: Komar
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authors.lastname: Kaca
authors.forename: J
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authors.lastname: Malejczyk
authors.forename: M
authors.initials: M
authors.lastname: Jakóbisiak