Prostaglandins: antiproliferative effect of PGD 2 on cultured human glioma cells

Five cultured human glioma cell lines were investigated for their reaction to prostaglandin (PG) D2 and E2. In all cases a suppressive effect on DNA synthesis as assessed by 3H-thymidine incorporation was seen with all test substances as early as six hours after the addition of the compounds in doses of usually 10(-5) M. A dose response curve was generated in four cases and showed an estimated ED 50 of about 5 X 10(-6)M. The effect was most pronounced at 12 hours after which the cultures began to recover except those which had been incubated with PGD2. In those cultures which had been exposed to PGD2 virtually no thymidine incorporation was seen after 24 hours and as long as 72 hours. In another set of experiments, the effect of PGD 2, PGE 2, two synthetic PGD 2 analogues, with a chlorine substitution in position 9 (DACl) or with a fluoride substitution in position 9 (DAF) and a synthetic prostacyclin-analogue (Iloprost) was investigated after single and repeated addition of the compounds. A second administration after 12 hours of incubation did not result in a further decrease in 3H-thymidine incorporation like that observed during that first incubation period. In general the cells recovered after 24 hours total incubation time except those which had received PGD 2 or repeated doses of PGE 2. Only in those cells which had been treated with PGD 2, an almost complete blockade of 3H-thymidine incorporation was seen even after the single administration. Parallel evaluation of the cells by flow cytometry showed effects on cell cycle distribution at different times of the incubation.(ABSTRACT TRUNCATED AT 250 WORDS)