Alterations of c-myc expression by antisense oligodeoxynucleotides enhance the induction of apoptosis in HL-60 cells.
This study was designed using c-myc antisense oligodeoxynucleoside phosphorothioate (AS PS-ODN) to evaluate how alterations of c-myc expression in HL-60 human myeloid leukemia cells could influence the induction of apoptosis. Unexpectedly both the continuous down-regulation of c-myc expression caused by exposure to c-myc AS PS-ODN and up-regulation after its withdrawal influenced apoptosis. We found that continuous suppression of c-myc expression by 10 microM c-myc AS PS-ODN could decrease the proliferation of HL-60 cells to approximately 60% of the control growth after 3 days of suspension culture, and when assessed morphologically the percentage of cells undergoing apoptosis was 3.5%. Evidence either of cell cycle arrest or cell cycle prolongation was not detected. It is likely that apoptosis induced by the sustained down-regulation of c-myc expression with AS PS-ODN treatment was solely sufficient to explain the inhibition of cell proliferation. Up-regulation of c-myc expression was observed within 1 h after c-myc AS PS-ODN withdrawal. This up-regulation further enhanced induction of apoptosis and involved up to 32% of the cells. These results suggest that while the continuous suppression of c-myc expression caused a constant effect on the induction of apoptosis, its abrupt up-regulation could rapidly drive a considerable number of HL-60 cells into the apoptotic pathway.
Kimura
S
S
Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan.
Maekawa
T
T
Hirakawa
K
K
Murakami
A
A
Abe
T
T
D017209:Apoptosis; D001483:Base Sequence; D002453:Cell Cycle; D002455:Cell Division; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism / Q000473:pathology*; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis / Q000502:physiology*; D014407:Tumor Cells, Cultured
D016376:Oligonucleotides, Antisense; D016271:Proto-Oncogene Proteins c-myc