Prostaglandins A and J arrest the cell cycle of cultured vascular smooth muscle cells without suppression of c- myc expression

Abstract

The effects of prostaglandins (PGs) A and J, which are antitumor eicosanoids, on the proliferation of cultured vascular smooth muscle cells were investigated. Serum-stimulated DNA synthesis was potently inhibited by PGA 1, PGA 2, PGJ 2, and δ 12-PGJ 2 in similar dose-dependent fashions. The effects of PGA 1 and PGA 2 were reversible when they were removed from the culture media, whereas recoveries were only partial in the cells treated with PGJ 2 and δ 12-PGJ 2. PGs were effective even if they were added immediately before entry into S phase. Inhibition of DNA synthesis was sustained when hydroxyurea, which blocks cell cycle at the G 1 S border, was added after the removal of PGA 2, and vice versa; PGs blocked DNA synthesis when they were added after the removal of hydroxyurea. Levels of c- myc mRNA formed two peaks during the G 1 phase, at 1–2 h and at 8–12 h. The PGs did not affect the first elevation, but enhanced the second and sustained it up to 18–24 h, whereas in controls, c- myc mRNA decreased quickly after entry into S phase. The rate of degradation of c- myc mRNA was much smaller in PG-treated cells than in nontreated cells. We conclude, therefore, that PGA and PGJ inhibit a crucial event(s) in the cell cycle occurring at the G 1 S border, but that this inhibition is not accompanied by the reduction in c- myc gene expression in contrast with some types of tumor cells treated With PGs.