E.: “A Summary of

The effects of the non-tumor-promoting protein kinase C (PKC) activator bryostatin 1 and the PKC inhibitors staurosporine and UCN-01 were examined with respect to modulation of 1-[b-D-arabinofuranosyl]cytosine (ara-C)-induced apoptosis in human myeloid leukemia cells (HL-60) overexpressing the antiapop-totic protein Bcl-2. HL-60/Bcl-2 cells displayed a 5-fold in-crease in Bcl-2 protein compared with empty-vector counter-parts (HL-60/pCEP4) but comparable levels of Bax, Mcl-1, and Bcl-xL. After exposure to an equimolar concentration of ara-C (10 mM for 6 hr), HL-60/Bcl-2 cells were significantly less sus-ceptible to apoptosis, DNA fragmentation, and loss of clono-genicity than HL-60/pCEP4 cells. The protective effect of in-creased Bcl-2 expression was manifested by a failure of ara-C to induce activation/cleavage of the Yama protease (CPP32; caspase-3) and degradation of one of its substrates, poly(ADP