Okadaic acid and dinophysistoxin-1, non-TPA-type tumor promoters, stimulate prostaglandin E2 production in rat peritoneal macrophages.
Okadaic acid and dinophysistoxin-1 isolated from a black sponge, Halichondria okadai are non-12-O-tetrade-canoylphorbol 13-acetate (non-TPA)-type tumor promoters of mouse skin. Okadaic acid at concentrations of 10-100 ng/ml stimulated prostaglandin E2 production in rat peritoneal macrophages. Dinophysistoxin-1 (35-methylokadaic acid) stimulated prostaglandin E2 production as strong as okadaic acid, but okadaic acid tetramethyl ether, an inactive compound as a tumor promoter, did not. Okadaic acid at 10 ng/ml (12.4 nM) stimulated prostaglandin E2 production as strongly as TPA at 10 ng/ml (16.2 nM) 20 h after incubation. Unlike TPA-type tumor promoters, okadaic acid required a lag phase before stimulation. The duration of this lag phase was dependent on the concentration of okadaic acid. Indomethacin inhibited okadaic acid-induced preostaglandin E2 production in a dose-dependent manner, and its inhibition was more strongly observed in okadaic acid-induced prostaglandin E2 production. Cycloheximide inhibited okadaic acid-induced release of radioactivity from [3H]arachidonic acid-labeled macrophages and prostaglandin E2 production dose dependently, suggesting that protein synthesis is a prerequisite for the stimulation of arachidonic acid metabolism. These results support our idea that tumor promoters, at very low concentrations, are able to stimulate arachidonic acid metabolism in rat peritoneal macrophages.
Ohuchi
K
K
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Tohoku University, Miyagi, Japan.
Tamura
T
T
Ohashi
M
M
Watanabe
M
M
Hirasawa
N
N
Tsurufuji
S
S
Fujiki
H
H
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002273:Carcinogens / Q000494:pharmacology*; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis*; D004988:Ethers, Cyclic / Q000494:pharmacology*; D007476:Ionophores / Q000494:pharmacology; D007700:Kinetics; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008387:Marine Toxins / Q000494:pharmacology; D019319:Okadaic Acid / Q000031:analogs & derivatives; D011714:Pyrans / Q000494:pharmacology*; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D001095:Arachidonic Acids; D002273:Carcinogens; D004988:Ethers, Cyclic; D007476:Ionophores; D008387:Marine Toxins; D011714:Pyrans; D019319:Okadaic Acid; D016718:Arachidonic Acid; C051904:dinophysistoxin 1; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate