Metabolic dehydration of prostaglandin E2 and cellular uptake of the dehydration product: correlation with prostaglandin E2-induced growth inhibition.
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.
Ohno
K
K
Fujiwara
M
M
Fukushima
M
M
Narumiya
S
S
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003470:Culture Media; D015232:Dinoprostone; D007939:Leukemia L1210 / Q000378:metabolism; D051379:Mice; D015230:Prostaglandin D2 / Q000031:analogs & derivatives*; D011454:Prostaglandins A / Q000378:metabolism; D011457:Prostaglandins D / Q000378:metabolism; D011458:Prostaglandins E / Q000378:metabolism*; D013696:Temperature; D013997:Time Factors; D014867:Water
D003470:Culture Media; D011454:Prostaglandins A; D011457:Prostaglandins D; D011458:Prostaglandins E; D014867:Water; C037112:9-deoxy-delta-9-prostaglandin D2; C100008:prostaglandin A2; D015232:Dinoprostone; D015230:Prostaglandin D2