Aspartate-based inhibitor of interleukin-1 beta-converting enzyme prevents antitumor agent-induced apoptosis in human myeloid leukemia U937 cells.
We found that a novel protease inhibitor, benzyloxycarbonyl-Asp-CH2OC(O)-2,6-dichlorobenzene (Z-Asp-CH2-DCB), which can preferentially inhibit interleukin-1 beta-converting enzyme (ICE), completely blocked the apoptotic cell death of human myeloid leukemia U937 cells caused by etoposide, camptothecin, 1-beta-D-arabinofuranosyl-cytosine and Adriamycin, as well as TNF-alpha, anti-Fas antibody and staurosporine. However, Z-Asp-CH2-DCB did not block non-apoptotic cell death of U937 cells caused by etoposide during prolonged incubation periods. These results indicate that ICE or ICE-like proteases inhibited by Z-Asp-CH2-DCB are involved in a common pathway of apoptotic cell death in U937 cells.
Mashima
T
T
Institute of Molecular and Cellular Biosciences, University of Tokyo, Japan.
Naito
M
M
Kataoka
S
S
Kawai
H
H
Tsuruo
T
T
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D002166:Camptothecin / Q000494:pharmacology; D020170:Caspase 1; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000494:pharmacology*; D003561:Cytarabine / Q000494:pharmacology; D004273:DNA, Neoplasm / Q000032:analysis / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D007951:Leukemia, Myeloid; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; C093260:benzyloxycarbonyl-Asp-CH2OC(O)-2,6-dichlorobenzene; D003561:Cytarabine; D001224:Aspartic Acid; D005047:Etoposide; D004317:Doxorubicin; D003546:Cysteine Endopeptidases; D020170:Caspase 1; D002166:Camptothecin