Role of adenosine 3'5'-cyclic monophosphate in antineoplastic effect of prostaglandins (PGE1, PGE2, PGD2 and PGA1) on human neuroblastoma cells.
To determine the role of adenosine 3'5'-cyclic monophosphate (cAMP) in the antineoplastic effect of prostaglandins (PGE1, PGE2, PGD2 and PGA1), we studied 2 cell lines of human neuroblastoma; i.e. GOTO and SK-N-DZ. PGE1 or E2 at 30 micrograms/ml and PGD2 or PGA1 at 5 micrograms/ml were cytotoxic to these neuroblastoma cells. In both cell lines, increase of intracellular cAMP was closely associated with E-type PGs cytotoxicity, however, in PGD2, or PGA1 cytotoxicity, cAMP increase was observed only in GOTO cells. Pretreatment of GOTO cells with 5 micrograms/ml PGE2 for 24 hr caused a desensitization of cAMP responses to PGE1, PGD2 or PGA1 only in association with a reduced cytotoxicity of PGE1. On the other hand, PGE2-pretreated SK-N-DZ cells resulted in a desensitization in response to PGE1, but not to other PGs, without affecting the cytotoxicity of these PGs. A decreased [3H]PGE1 binding similarly occurred in either the PGE2-pretreated GOTO or SK-N-DZ cells. However, cholera toxin- or forskolin-induced cAMP production was suppressed only in the pretreated GOTO cells. cAMP response by forskolin rather increased in the pretreated SK-N-DZ cells. These results indicate that antineoplastic effect of E type PGs mediates through cAMP, but not that of PGD2 and PGA1 and that PGE2 pretreatment may cause a down regulation of PGE1 receptor site in both cell lines. It is also suggested that PGE2 pretreatment results in a heterologous desensitization in GOTO and a homologous desensitization in SK-N-DZ cells.
Hashida
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T
Department of Pediatrics, Kyoto Prefectural University of Medicine, Japan.
Todo
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Imashuku
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D000527:Alprostadil / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism / Q000502:physiology*; D015232:Dinoprostone / Q000494:pharmacology; D004351:Drug Resistance; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D006801:Humans; D009447:Neuroblastoma / Q000473:pathology*; D015230:Prostaglandin D2 / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology*; D011454:Prostaglandins A / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D011453:Prostaglandins; D011454:Prostaglandins A; D005576:Colforsin; D002772:Cholera Toxin; D000242:Cyclic AMP; D000527:Alprostadil; D015232:Dinoprostone; D015230:Prostaglandin D2; C100573:prostaglandin A1