APOPTOSIS INDUCED IN L1210 LEUKEMIA-CELLS BY AN INHIBITOR OF THE CHYMOTRYPSIN-LIKE ACTIVITY OF THE PROTEASOME

Of a number of factors involved in apoptosis, protease activity may pl ay a crucial role. We show that -benzyloxycarbonyl-IIe-Glu(O-t-butyl)- Ala-leucinal (PSI), a selective inhibitor of the chymotrypsin-like act ivity of the proteasome, induces massive apoptosis in murine leukaemia L1210 cells. At 50 nM concentration, PSI induces a block of cytokines is, while higher concentrations (500 nM) cause S phase block and massi ve apoptosis. Z-Leu-leucinal, a specific calpain inhibitor, did not in duce apoptosis. In contrast to previous reports, TNF-alpha did not enh ance apoptosis when combined with PSI. Our results suggest that protea some inhibitors may be considered as potential anti-neoplastic agents.