PGJ2 and delta 12PGJ2 inhibit cell growth accompanied with inhibition of phosphoinositide turnover in human astrocytoma cells.
PGJ2 and delta 12PGJ2 (1 microM to 30 microM) inhibited the growth of human astrocytoma cells (1321N1) in a time-dependent manner within 48 hrs, determined by [3H]thymidine incorporation into acid-insoluble fraction or amounts of protein. The EC50 values for PGJ2 and delta 12PGJ2 were approximately 8 microM and 6 microM, respectively. [3H]Thymidine incorporation to acid insoluble fraction was inhibited by these PGs within 1 hr, indicating that these PGs rapidly affect cell functions. Although it has been reported that an increase in cyclic AMP inhibits cell growth, PGJ2 and delta 12PGJ2, but not PGE1, reduced isoproterenol (10 microM)-induced accumulation of cyclic AMP, suggesting that PGJ2 and delta 12PGJ2 may disturb adenylate cyclase system, which might be independent on cell growth. On the other hand, these PGs inhibited the incorporation of [3H]inositol into phospholipid fraction within 6 hrs. Furthermore, PGJ2 and delta 12PGJ2 inhibited carbachol- and/or histamine-induced accumulation of inositol phosphates with a similar dose-dependency to their inhibitions of cell growth. In membrane preparations, however, PGJ2 and delta 12PGJ2 failed to inhibit GTP gamma S (10 microM)- nor Ca2+ (1 mM)-induced accumulation of inositol phosphates. The site of PGJ2 or delta 12PGJ2 in inhibition of inositol phosphate accumulation would not be phospholipase C nor a putative GTP binding protein involved in activation of phospholipase C. The present results indicate that PGJ2 and delta 12PGJ2 inhibit cell growth in human astrocytoma cells and the inhibition of phosphoinositide turnover by these PGs might be involved in the inhibition of cell growth.
Nakahata
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Department of Pharmacology, Fukushima Medical College, Japan.
Abe
M T
MT
Nakanishi
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D001254:Astrocytoma / Q000378:metabolism / Q000473:pathology*; D002217:Carbachol / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D019204:GTP-Binding Proteins / Q000502:physiology; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D007294:Inositol / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D010716:Phosphatidylinositols / Q000378:metabolism*; D015230:Prostaglandin D2 / Q000494:pharmacology* / Q000031:analogs & derivatives; D014407:Tumor Cells, Cultured
D010716:Phosphatidylinositols; D007294:Inositol; C037112:9-deoxy-delta-9-prostaglandin D2; D006632:Histamine; C040810:9-deoxy-9,10-didehydro-12,13-didehydro-13,14-dihydroprostaglandin D2; D002217:Carbachol; D004247:DNA; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D007545:Isoproterenol; D015230:Prostaglandin D2