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A Requirement for Protein Kinase C Inhibition for Calcium-triggered Apoptosis in Acute Lymphoblastic Leukemia Cells¹

Departments of Immunology [D-M. Z., W-H. F.], Experimental Oncology [R. K. N., F. M. U.], and Drug Discovery Program [F. M. U.], Hughes Institute, St. Paul, Minnesota 55113

ABSTRACT

We have evaluated the cytotoxicities of the combinations of calcium mobilizers and PKC inhibitors against human acute lymphoblastic leukemia (ALL) cells. Here we report that calcium mobilizers alone or PKC inhibitors alone do not induce apoptosis in human ALL cells. However, the combinations of calcium 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 trigger an apoptotic calcium signal in ALL cells. The exquisite sensitivity of ALL cells to calcium-dependent apoptosis in the presence of PKC inhibitors could provide the basis for new treatment programs against ALL.

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