Daunorubicin inhibits gene expression of cyclooxygenase-2 in vascular smooth muscle cells.
Daunorubicin (0.1-1 microM) concentration-dependently inhibited prostacyclin production induced by interleukin-1beta (IL-1beta, 2.5 ng/ml) in cultured aortic smooth muscle cells isolated from rats. IL-1beta stimulation caused activation of nuclear factor-kappaB (NF-kappaB) and expression of cyclooxygenase-2 (COX-2) mRNA and protein, which were inhibited by daunorubicin. However, COX activity, evaluated by conversion of exogenous arachidonic acid to prostacyclin, was not affected by daunorubicin (0.1-1 microM). Protein expression of COX-1 and NF-kappaB was not affected by daunorubicin. Daunorubicin also inhibited nitric oxide (NO) production induced by IL-1beta. These results suggest that daunorubicin attenuated prostacyclin synthesis through inhibiting expression of COX-2 mRNA, which could be explained by perturbation of NF-kappaB activation.
Yasui
K
K
Department of Hygiene and Preventive Medicine, School of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan.
Wakabayashi
I
I
Negoro
M
M
Suehiro
A
A
Kakishita
E
E
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001011:Aorta; D051546:Cyclooxygenase 2; D003630:Daunorubicin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015870:Gene Expression / Q000187:drug effects; D007375:Interleukin-1 / Q000494:pharmacology; D007527:Isoenzymes / Q000235:genetics*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology*; D016328:NF-kappa B / Q000096:biosynthesis / Q000187:drug effects; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D051381:Rats
D000903:Antibiotics, Antineoplastic; D007375:Interleukin-1; D007527:Isoenzymes; D016328:NF-kappa B; D009569:Nitric Oxide; D011464:Epoprostenol; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D003630:Daunorubicin