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 μg/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 μg/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 μg/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.