Requirements for protein synthesis and calcium for stimulation of prostaglandin synthesis in cultured rat liver cells by tumor promoters.
The tumor promoters, 12-O-tetradecanoylphorbol-13-acetate (TPA), phorbol-12,13-didecanoate, teleocidin, and dihydroteleocidin, at nM levels, but not the non-tumor-promoting 4 alpha-phorbol-12,13-didecanoate even at microM concentrations, stimulated arachidonic acid metabolism in cultured rat liver cells. These liver cells synthesize primarily prostaglandin I2 [measured as its nonenzymatic hydrolytic product, 6-keto-prostaglandin F1 alpha (PGF1 alpha)]. The production of 6-keto-PGF1 alpha increased with time of incubation with TPA and was essentially complete in 4 hr. Cycloheximide, at nM levels, blocked the TPA-stimulated 6-keto-PGF1 alpha production in a dose-dependent manner; this inhibition was related to inhibition of protein synthesis. Chelation of Ca2+ by ethyleneglycol-bis(beta-aminoethyl ether)-N,N'-tetraacetic acid, treatment of the cells with the Ca2+ channel blocker, nifedipine, or inhibition of intracellular Ca2+ mobilization by 8-(diethylamine)octyl-3,4, 5-trimethoxybenzoate hydrochloride also inhibited TPA-stimulated 6-keto-PGF1 alpha production. The steroidal antiinflammatory drug, dexamethasone, a potent in vivo inhibitor of tumor promotion, was an inhibitor of 6-keto-PGF1 alpha stimulation by TPA.
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002273:Carcinogens / Q000494:pharmacology*; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008235:Lyngbya Toxins; D010703:Phorbol Esters / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis*; D014176:Protein Biosynthesis; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000470:Alkaloids; D002273:Carcinogens; D008235:Lyngbya Toxins; D010703:Phorbol Esters; D011453:Prostaglandins; C008876:phorbol-12,13-didecanoate; C022176:teleocidins; D003907:Dexamethasone; C022229:dihydroteleocidin B; D003513:Cycloheximide; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium