TY - JOUR
T1 - Apoptosis induced in L1210 leukaemia cells by an inhibitor of the chymotrypsin-like activity of the proteasome
AU - Wójcik, C.
AU - Stoklosa, T.
AU - Giermasz, A.
AU - Golab, J.
AU - Zagozdzon, R.
AU - Kawiak, J.
AU - Wilk, S.
AU - Komar, A.
AU - Kaca, A.
AU - Malejczyk, J.
AU - Jakóbisiak, M.
N1 - Funding Information:
This research was partly supported by D31 and D37 statutory grants of the Warsaw Medical School and NIH grant NS 29936 to S. Wilk. T. Stoklosa is a recipient of the Foundation for Polish Science Award.
PY - 1997
Y1 - 1997
N2 - Of a number of factors involved in apoptosis, protease activity may play a crucial role. We show that N-benzyloxycarbonyl-IIe-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-α did not enhance apoptosis when combined with PSI. Our results suggest that proteasome inhibitors may be considered as potential anti-neoplastic agents.
AB - Of a number of factors involved in apoptosis, protease activity may play a crucial role. We show that N-benzyloxycarbonyl-IIe-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-α did not enhance apoptosis when combined with PSI. Our results suggest that proteasome inhibitors may be considered as potential anti-neoplastic agents.
KW - Apoptosis
KW - Experimental cancer therapy
KW - L1210 leukaemia
KW - Proteasome, proteasome inhibitor, TNF
UR - http://www.scopus.com/inward/record.url?scp=2342517449&partnerID=8YFLogxK
U2 - 10.1023/A:1026470027387
DO - 10.1023/A:1026470027387
M3 - Article
AN - SCOPUS:2342517449
SN - 1360-8185
VL - 2
SP - 455
EP - 462
JO - Apoptosis : an international journal on programmed cell death
JF - Apoptosis : an international journal on programmed cell death
IS - 5
ER -