Apoptosis induced in L1210 leukaemia cells by an inhibitor of the chymotrypsin-like activity of the proteasome.
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.
Wójcik
C
C
Laboratory for Molecular Cell Biology, Department of Histology and Embryology, Institute of Biostructure, Warsaw Medical School, Poland. cwojcik@ib.amwaw.edu.pl
Stoklosa
T
T
Giermasz
A
A
Golab
J
J
Zagozdzon
R
R
Kawiak
J
J
Wilk
S
S
Komar
A
A
Kaca
A
A
Malejczyk
J
J
Jakóbisiak
M
M