Okadaic acid and dinophysistoxin-1, non-TPA-type tumor promoters, stimulate prostaglandin E2 production in rat peritoneal macrophages

Kazuo Ohuchi, Toshiya Tamura, Mariko Ohashi, Masako Watanabe, Noriyasu Hirasawa, Susumu Tsurufuji, Hirota Fujiki

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26 Citations (Scopus)


Okadaic acid and dinophysistoxin-1 isolated from a black sponge, Halichondria okadai are non-12-O-tetradecanoylphorbol 13-acetate (non-TPA)-type tumor promoters of mouse skin. Okadaic acid at concetrations 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.

Original languageEnglish
Pages (from-to)86-91
Number of pages6
JournalBBA - Molecular Cell Research
Issue number1
Publication statusPublished - 1989 Sep 4


  • (Rat peritoneal macrophage)
  • Dinophysistoxin-1
  • Okadaic acid
  • Prostaglandin E
  • Tumor promoter

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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