When L-1210 murine
leukemia cells were incubated with 60 microM
PGE2 in culture medium containing
fetal calf serum for various time, cell proliferation was inhibited dependent on incubation time. However, when the medium containing
PGE2 was changed every 6 h during 24 h exposure to cells, growth inhibition became much weaker. Moreover, when the medium containing
PGE2 was aged by preincubating without cells at 37 degrees C, growth inhibitory effect of the medium was enhanced with preincubation time, suggesting that active growth inhibitory compound(s) accumulated during preincubation. In culture medium containing
fetal calf serum,
PGE2 degraded time-dependently and the major product was identified as
PGA2 by HPLC. Furthermore, when cells were incubated with the medium containing 60 microM[3H]
PGE2 or the same medium aged by preincubation, we observed that the radioactivity was taken up by the cells time-dependently, and identified the incorporated radioactivity as
PGA2. This uptake was closely correlated with decrease in viable cell number during incubation. These results suggested that growth inhibitory effect of
PGE2 was due to the metabolic
dehydration of
PGE2 to
PGA2, and
PGA2, after taken up by cells, exerted cell growth inhibition.