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 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.
Department of Immunology, Hughes Institute, St. Paul, Minnesota 55113, USA.
D M
DM
Zhu
W H
WH
Fang
R K
RK
Narla
F M
FM
Uckun
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism*; D002227:Carbazoles / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D007527:Isoenzymes / Q000096:biosynthesis; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D002227:Carbazoles; D004791:Enzyme Inhibitors; D007211:Indoles; D007527:Isoenzymes; C081021:Go 6976; D011493:Protein Kinase C; D002118:Calcium