Apoptosis induced in L1210 leukaemia cells by an inhibitor of the chymotrypsin-like activity of the proteasome

C. Wójcik; T. Stoklosa; A. Giermasz; J. Golab; R. Zagozdzon; J. Kawiak; S. Wilk; A. Komar; A. Kaca; J. Malejczyk; M. Jakóbisiak

doi:10.1023/A:1026470027387

Apoptosis induced in L1210 leukaemia cells by an inhibitor of the chymotrypsin-like activity of the proteasome

C. Wójcik, T. Stoklosa, A. Giermasz, J. Golab, R. Zagozdzon, J. Kawiak, S. Wilk, A. Komar, A. Kaca, J. Malejczyk, M. Jakóbisiak

Research output: Contribution to journal › Article › peer-review

26 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	455-462
Number of pages	8
Journal	Apoptosis
Volume	2
Issue number	5
DOIs	https://doi.org/10.1023/A:1026470027387
State	Published - 1997
Externally published	Yes

Keywords

Apoptosis
Experimental cancer therapy
L1210 leukaemia
Proteasome, proteasome inhibitor, TNF

ASJC Scopus subject areas

Pharmacology
Pharmaceutical Science
Clinical Biochemistry
Cell Biology
Biochemistry, medical
Cancer Research

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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-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.",

keywords = "Apoptosis, Experimental cancer therapy, L1210 leukaemia, Proteasome, proteasome inhibitor, TNF",

author = "C. W{\'o}jcik and T. Stoklosa and A. Giermasz and J. Golab and R. Zagozdzon and J. Kawiak and S. Wilk and A. Komar and A. Kaca and J. Malejczyk and M. Jak{\'o}bisiak",

note = "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.",

year = "1997",

doi = "10.1023/A:1026470027387",

language = "English (US)",

volume = "2",

pages = "455--462",

journal = "Apoptosis",

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publisher = "Springer Netherlands",

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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

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DO - 10.1023/A:1026470027387

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SN - 1360-8185

VL - 2

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JO - Apoptosis

JF - Apoptosis

IS - 5

ER -

Apoptosis induced in L1210 leukaemia cells by an inhibitor of the chymotrypsin-like activity of the proteasome

Abstract

Keywords

ASJC Scopus subject areas

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