STIMULATION OF PROSTAGLANDIN-E(2) PRODUCTION AND INDUCTION OF SPECIFIC PROTEIN-SYNTHESIS IN RAT PERITONEAL-MACROPHAGES BY A TUMOR PROMOTER STAUROSPORINE
T. Tamura et al., STIMULATION OF PROSTAGLANDIN-E(2) PRODUCTION AND INDUCTION OF SPECIFIC PROTEIN-SYNTHESIS IN RAT PERITONEAL-MACROPHAGES BY A TUMOR PROMOTER STAUROSPORINE, Journal of cancer research and clinical oncology, 120(1-2), 1993, pp. 5-11
Staurosporine is a microbial anti-fungal alkaloid having potent inhibi
tory activity on protein kinase C and is a non 12-O-tetradecanoylphorb
ol-13-acetate-type tumor promoter in two-stage carcinogenesis experime
nts in mouse skin. Effects of staurosporine and its structurally relat
ed compounds K-252a, KT5720 and KT5822 on prostaglandin E2 production,
release of arachidonic acid from membrane phospholipids, and uptake o
f [S-35]methionine into intracellular proteins were examined in rat pe
ritoneal macrophages. Among the four compounds, only staurosporine sti
mulated the production of prostaglandin E2 and release of arachidonic
acid at concentrations of 1 ng/ml and 10 ng/ml. The uptake of [S-35]me
thionine into cellular proteins, estimated to be 120 kDa and 125 kDa m
olecular mass, was also stimulated by staurosporine treatment, and the
uptake was increased in parallel with the increase in prostaglandin E
2 production. At higher concentrations (100 ng/ml and 1000 ng/ml), sta
urosporine inhibited prostaglandin E2 production and did not induce th
e specific protein synthesis. Other compounds neither stimulated prost
aglandin E2 production nor induced specific protein synthesis. K-252a
inhibited prostaglandin E2 production at concentrations above 10 ng/ml
. These results suggest that the staurosporine-induced proteins might
participate in the tumor promotion or at least in the staurosporine-in
duced stimulation of prostaglandin E2 production.