ASPARTATE-BASED INHIBITOR OF INTERLEUKIN-1-BETA-CONVERTING ENZYME PREVENTS ANTITUMOR AGENT-INDUCED APOPTOSIS IN HUMAN MYELOID-LEUKEMIA U937CELLS

We found that a novel protease inhibitor, enzyloxycarbonyl-Asp-CH2OC(O )-2,6,-dichlorobenzene (Z-Asp-CH2-DCB), which can preferentially inhib it interleukin-1 beta-converting enzyme (ICE), completely blocked the apoptotic cell death of human myeloid leukemia U937 cells caused by et oposide, camptothecin, 1-beta-D-arabinofuranosyl-cytosine and Adriamyc in, 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 c aused 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. ( C) 1995 Academic Press, Inc.