A requirement for protein kinase C inhibition for calcium-triggered apoptosis in acute lymphoblastic leukemia cells

We have evaluated the cytotoxicities of the combinations of calcium mobiliz ers and PKC inhibitors against human acute lymphoblastic leukemia (ALL) cel ls. Here we report that calcium mobilizers alone or PKC inhibitors alone do not induce apoptosis in human ALL cells, However, the combinations of calc ium mobilizers with potent inhibitors of PKC cause significant apoptosis in ALL cells. Our results provide experimental evidence that PKC blocks Ca2+- triggered apoptosis in human ALL cells. Thus, PKC inhibitors can be used to enhance the antileukemic activity of chemical or biological agents that tr igger an apoptotic calcium signal in ALL cells. The exquisite sensitivity o f ALL cells to calcium-dependent apoptosis in the presence of PKC inhibitor s could provide the basis for new treatment programs against ALL.