AUGMENTATION BY APHIDICOLIN OF 1-BETA-D-ARABINOFURANOSYLCYTOSINE-INDUCED C-JUN AND NF-KAPPA-B ACTIVATION IN A HUMAN MYELOID-LEUKEMIA CELL-LINE - CORRELATION WITH APOPTOSIS

1-beta-D-arabinofuranosylcytosine (ara-C) (2 mu M) can induce apoptosi s in a human myeloid leukemia cell line, U937, after 4 h of incubation . Pretreatment of cells with aphidicolin (2 mu M) augments ara-C-induc ed apoptosis, since it was first observed at 0.4 mu M ara-C and became more intense at 2 and 10 mu M. Although aphidicolin itself had a marg inal effect on c-jun expression, it significantly augmented ara-C indu ced c-jun upregulation by shortening the lag time and lowering ara-C c oncentrations necessary for the induction of detectable c-jun transcri pts. Aphidicolin and ara-C acted synergistically to increase NF-kappa B DNA binding activity as determined by an electrophoretic mobility sh ift assay. Expression of c-myc was slightly increased through the DNA degradative phase, and was then downregulated. Thus, the activation of NF-kappa B and c-jun expression seems to be well correlated with the potentiation by aphidicolin of ara-C-induced apoptosis.