Effects of antitumor agents on inducible prostacyclin production in vascular smooth muscle.
The effects of various antitumor agents were examined on prostacyclin production induced by interleukin-1beta in rat aortic smooth muscle cells. Stimulation of the cells with interleukin-1beta (2.5 ng/ml) resulted in a great increase of prostacyclin production, which was abolished by indomethacin (1 microM) or cycloheximide (2 microM). Daunorubicin at 0.1-1 microM inhibited the inducible prostacyclin production in a concentration-dependent manner. However, other antitumor agents (cyclophosphamide at 1-100 microM, 5-fluorouracil at 1-100 microM and vincristine at 1-100 nM) tested did not significantly affect it. Protein expression of cyclooxygenase-2 induced by interleukin-1beta was inhibited by daunorubicin at 0.1-1 microM, but was not affected by other antitumor agents. These results suggest that daunorubicin inhibits induction of cyclooxygenase-2 and subsequent prostacyclin production in rat aortic smooth muscle cells.
Yasui
K
K
Department of Hygiene and Preventive Medicine, School of Medicine, Yamagata University, Japan.
Suehiro
A
A
Kakishita
E
E
Wakabayashi
I
I
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology*; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D003630:Daunorubicin / Q000009:adverse effects / Q000494:pharmacology; D011464:Epoprostenol / Q000378:metabolism*; D007375:Interleukin-1; D007527:Isoenzymes / Q000187:drug effects / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D000970:Antineoplastic Agents; D007375:Interleukin-1; D007527:Isoenzymes; D011464:Epoprostenol; D007770:L-Lactate Dehydrogenase; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D003630:Daunorubicin