Inhibitory effects of prostaglandin A2 on c-myc expression and cell cycle progression in human leukemia cell line HL-60.
The effect of prostaglandin A2 (PGA2) on c-myc expression was investigated in a human promyelocytic leukemia cell line, HL-60, which responded to PGA2 with a dose-dependent growth inhibition. Northern blot analysis indicated that treatment with PGA2 at 0.5 to 5.0 micrograms/ml remarkably reduced the steady state level of c-myc mRNA within 3 h, and then it gradually recovered according to the order of concentration of the drug. In contrast to c-myc, the level of class I HLA mRNA, as an internal control, was not diminished by PGA2 treatment. Further, this reduction of c-myc was not disturbed by cycloheximide, suggesting that this PGA2 action on c-myc expression is independent of de novo protein synthesis. Cytofluorometric analysis revealed that the exposure of HL-60 cells to PGA2 at 0.5 or 5.0 micrograms/ml arrested the cells in the G0-G1 phase of the cell cycle. This accumulation of the cells in G0-G1 phase continues until 24 or 36 h at 0.5 or 5.0 micrograms/ml, respectively. The G0-G1 arrest of the cell cycle was also recovered as the inhibition of c-myc was released. This recovery may be due to the loss of activity of PGA2 in culture medium. This study clearly showed that PGA2 treatment arrested HL-60 cells in the G0-G1 phase of the cell cycle and was associated with the reduction of c-myc mRNA.
Ishioka
C
C
Department of Clinical Cancer Chemotherapy, Tohoku University, Sendai, Japan.
Kanamaru
R
R
Sato
T
T
Dei
T
T
Konishi
Y
Y
Asamura
M
M
Wakui
A
A
D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D005434:Flow Cytometry; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D015230:Prostaglandin D2 / Q000031:analogs & derivatives; D011454:Prostaglandins A / Q000494:pharmacology*; D011457:Prostaglandins D / Q000494:pharmacology; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured
D006680:HLA Antigens; D011454:Prostaglandins A; D011457:Prostaglandins D; D012333:RNA, Messenger; C040810:9-deoxy-9,10-didehydro-12,13-didehydro-13,14-dihydroprostaglandin D2; D003513:Cycloheximide; C100008:prostaglandin A2; D015230:Prostaglandin D2