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 microM) can induce apoptosis in a human myeloid leukemia cell line, U937, after 4 h of incubation. Pretreatment of cells with aphidicolin (2 microM) augments ara-C-induced apoptosis, since it was first observed at 0.4 microM ara-C and became more intense at 2 and 10 microM. Although aphidicolin itself had a marginal effect on c-jun expression, it significantly augmented ara-C induced c-jun upregulation by shortening the lag time and lowering ara-C concentrations necessary for the induction of detectable c-jun transcripts. Aphidicolin and ara-C acted synergistically to increase NF-kappa B DNA binding activity as determined by an electrophoretic mobility shift 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.
Kuwakado
K
K
Department of Pediatrics, Faculty of Medicine, Kyoto University, Japan.
Kubota
M
M
Bessho
R
R
Kataoka
A
A
Usami
I
I
Lin
Y W
YW
Okuda
A
A
Wakazono
Y
Y
D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D016590:Aphidicolin / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D003561:Cytarabine / Q000008:administration & dosage*; D004249:DNA Damage / Q000187:drug effects; D004257:DNA Polymerase II / Q000037:antagonists & inhibitors*; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016758:Genes, jun; D016259:Genes, myc; D006801:Humans; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000235:genetics*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D004791:Enzyme Inhibitors; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D003561:Cytarabine; D016590:Aphidicolin; D004257:DNA Polymerase II