Augmentation by aphidicolin of 1-β-d-arabinofuranosylcytosine-induced c-jun and NF-κB activation in a human myeloid leukemia cell line: Correlation with apoptosis

Autor: Ying Wei Lin, Akihiro Kataoka, Akiro Okuda, Katsuji Kuwakado, Ikuya Usami, Rikimaru Bessho, Yoshihiro Wakazono, Masaru Kubota
Rok vydání: 1995
Předmět:
Zdroj: Leukemia Research. 19:645-650
ISSN: 0145-2126
DOI: 10.1016/0145-2126(95)00046-q
Popis: 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.
Databáze: OpenAIRE