Sesquiterpene lactone suppresses vascular smooth muscle cell proliferation and migration via inhibition of cell cycle progression.
Abnormal vascular smooth muscle cell (VSMC) proliferation and migration are involved in restenosis following percutaneous transluminal angioplasty (PTCA) as well as in the development and progression of atherosclerosis. We investigated the mechanisms underlying the inhibitory effect of the sesquiterpene 3-oxo-5alphaH,8betaH-eudesma-1,4(15),7(11)-trien-8,12-olide (1) on rat VSMC proliferation and migration. VSMCs were isolated from rat aorta, and then the effect of 1 on cell proliferation and migration was examined using methylthiazolyldiphenyl-tetrazolium bromide (MTT) and chemotaxis assays, respectively. Compound 1 had a potent inhibitory effect on fetal calf serum-induced VSMC proliferation. This effect correlated with reduced expression of cyclin D(1). In addition, 1 also inhibited platelet derived growth factor (PDGF)-induced migration of VSMCs. These results indicate that 1 is a promising candidate for additional biological evaluation to further define its potential as an inhibitory modulator of VSMC responses that contribute to restenosis following PTCA and to the development and progression of atherosclerosis.
Nakagawa
Munehiro
M
Second Department of Internal Medicine, Gifu University School of Medicine, Gifu 501-1194, Japan.
Ohno
Takamasa
T
Maruyama
Rumi
R
Okubo
Munenori
M
Nagatsu
Akito
A
Inoue
Makoto
M
Tanabe
Hiroki
H
Takemura
Genzou
G
Minatoguchi
Shinya
S
Fujiwara
Hisayoshi
H
D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D019938:Cyclin D1 / Q000096:biosynthesis; D003864:Depression, Chemical; D016193:G1 Phase / Q000187:drug effects; D007202:Indicators and Reagents; D007783:Lactones / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012717:Sesquiterpenes / Q000494:pharmacology*; D013778:Tetrazolium Salts; D013844:Thiazoles