Cyclooxygenase-independent inhibition of smooth muscle cell mitogenesis by ibuprofen.
The aryl-propionic acid derivative, ketoprofen, has been shown to inhibit fibroblast growth by a cylooxygenase-dependent mechanism [Sánchez, T., Moreno, J.J., 1999. S(+) enantiomer inhibits prostaglandin production and cell growth in 3T6 fibroblast cultures. Eur. J. Pharmacol. 370, 63-67]. The present study demonstrates that ibuprofen, another aryl-propionic acid derivative, inhibited platelet-derived growth factor-BB (20 ng/ml)-induced mitogenesis of cultured bovine coronary artery smooth muscle cells in a stereo-independent manner. In addition, pretreatment of the cells with indomethacin (3 microM) did not affect the inhibitory effects of ibuprofen enantiomers on smooth muscle cell mitogenesis. Thus, aryl-propionic acid-type cyclooxygenase inhibitors can inhibit cell proliferation by both, cyclooxygenase-dependent and -independent ways.
Weber
A
A
Institut für Pharmakologie und Klinische Pharmakologie, Moorenstr. 5, D-40225 Heinrich-Heine-Universität, Düsseldorf, Germany.
Yildirim
H
H
Schrör
K
K
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D000077214:Becaplermin; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D007052:Ibuprofen / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors; D020574:Proto-Oncogene Proteins c-sis; D013237:Stereoisomerism
D016861:Cyclooxygenase Inhibitors; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D015121:6-Ketoprostaglandin F1 alpha; D004247:DNA; D007052:Ibuprofen; D007213:Indomethacin