Antiproliferative effect in rat vascular smooth muscle cells by osthole, isolated from Angelica pubescens

Jih Hwa Guh, Sheu Meei Yu, Feng Nien Ko, Tian Shung Wu, Che Ming Teng

研究成果: Article同行評審

57 引文 斯高帕斯(Scopus)


The antiproliferative effect of osthole on rat vascular smooth muscle cells was examined in this study. A number of mitogenic agents, e.g., foetal-calf serum (10%, v/v) and platelet-derived growth factor (20 ng/ml), and pharmacological agents, e.g., serotonin (10 μM), ionomycin (3 nM), phorbol 12,13-dibutyrate (20 nM) and phorbol myristate acetate (200 nM), were used to induce DNA synthesis in rat vascular smooth muscle cells; these effects were concentration dependently inhibited by osthole and the half-maximal inhibition (IC50) occurred at 13.6 ± 1.8, 11.8 ± 1.3, 7.9 ± 0.9, 7.1 ± 0.2, 7.8 ± 0.2 and 8.6 ± 0.4 μM, respectively. Osthole itself increased the cyclic AMP and cyclic GMP formations in a concentration-dependent manner; it synergistically increased cyclic AMP and cyclic GMP levels induced by forskolin and sodium nitroprusside, respectively. After 48 h deprivation of serum, cells were re-stimulated with serum and the cell cycle was observed by flow cytometry; treatment of cells with osthole (100 μM) caused a block of serum-inducible cell cycle progression at a point before the G1-S boundary. The addition of osthole (100 μM) at various times after serum addition to serum-deprived cells showed full inhibition of DNA synthesis even when added 6 h after serum. The cell cycle progression block was gradually lost as the delay from serum to osthole application was increased from 6 to 18 h. The effect of osthole on serum-stimulated [3H]thymidine incorporation into endothelial cells was examined and the IC50 value (158.7 ± 2.7 μM, n = 6) was obtained; it exhibited greater potency (12-fold) for vascular smooth muscle cells as compared with endothelial cells as an antiproliferative agent. These results suggest that osthole is a selective antiproliferative agent in vascular smooth muscle cells. The antiproliferative effect occurs at the early G, phase of the cell cycle and is due to the increase in cyclic AMP and cyclic GMP contents.

頁(從 - 到)191-197
期刊European Journal of Pharmacology
出版狀態Published - 1996 三月 7

All Science Journal Classification (ASJC) codes

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