Dual effects of staurosporine on arachidonic acid metabolism in rat peritoneal macrophages

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

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

Staurosporine is a microbial anti-fungal alkaloid having a most potent inhibitory activity on protein kinase C and is recently found as a non-12-O-tetradecanoylphorbol-13-acetate (non-TPA)-type tumor promoter of mouse skin, although tumor promotion induced by a TPA-type tumor promoter teleocidin is suppressed by staurosporine. When rat peritoneal macrophages were incubated in the medium containing various concentrations of staurosporine, prostaglandin E2 production and release of radioactivity from [3H]arachidonic acid-labeled macrophages were stimulated at concentrations of 1 and 10 ng/ml. But higher concentrations of staurosporine such as 100 and 1000 ng/ml showed no stimulative effect on prostaglandin E2 production although cytoplasmic free calcium levels were increased in a dose-dependent manner. Staurosporine-induced stimulation of prostaglandin E2 production was inhibited by treatment with cycloheximide, suggesting that a certain protein synthesis is prerequisite for the stimulation of arahcidonic acid metabolism. At higher concentrations (100 and 1000 ng/ml), staurosporine inhibited TPA-type tumor promoter (TPA, teleocidin and aplysiatoxin)-induced stimulation of arachidonic acid metabolism probably due to the inhibition of protein kinases. Tumor promotion activity and anti-tumor promotion activity of staurosporine might be explained by the fact that the lower concentrations of staurosporine stimulate arachidonic acid metabolism and the higher concentrations of staurosporine inhibit the tumor promoter-induced arachidonic acid metabolism, respectively.

Original languageEnglish
Pages (from-to)141-147
Number of pages7
JournalBiochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism
Volume1047
Issue number2
DOIs
Publication statusPublished - 1990 Nov 12

Keywords

  • (Rat peritoneal macrophage)
  • Arachidonic acid
  • Cycloheximide
  • Phorbol ester
  • Prostaglandin E
  • Staurosporine
  • Tumor promoter

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Endocrinology

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