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.