Cell kinetic studies of PGD2 cytotoxicity on the in vitro growth of human neuroblastoma.
To determine the mechanism of the antineoplastic effect of PGD2, we studied the intracellular adenosine 3',5'-cyclic monophosphate (cAMP), cell growth and the kinetics of a human neuroblastoma (NCG line) in culture. Cells were maintained in RPMI 1640 with 10% FCS. cAMP level was determined for the cells, which were incubated for 10 min. with and without PGD2 (1 microgram/ml) in the presence of 100 microM papaverine. Growth inhibition was examined by counting viable cells after treatment with PGD2 (0-100 micrograms/ml) for 4 consecutive days starting at Day 4 after subculture. Effects on cell kinetics were examined for similarly treated cells by DNA cytofluorometry combined with 3H-thymidine autoradiography. In response to PGD2, the NCG line failed to increase its cAMP; however, cell growth was inhibited (IC50 13 micrograms/ml), accompanied by the marked decrease of S phase cells. The results indicate that PGD2 exerts its cytotoxic effect by a probable G1 block of the cell cycle and not through cAMP action.
D000970:Antineoplastic Agents; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007700:Kinetics; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015230:Prostaglandin D2; D011457:Prostaglandins D / Q000494:pharmacology*
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D011457:Prostaglandins D; D000242:Cyclic AMP; D015230:Prostaglandin D2