- 作者: Shiow-Lin Pan a, Jih-Hwa Guh b, Ying-Wen Huang a, Ya-Ling Chang a, Chiung-Yun Chang c, Li-Jiau Huang c, Sheng-Chu Kuo c, Che-Ming Teng a
- 作者服務機構: a Pharmacological Institute, b school of Pharmacy, College of Medicine, National Taiwan University, Taipei, c Graduate Institute of Pharmaceutical Chemistry, China Medical College, Taichung, Taiwan, ROC
- 中文摘要: --
- 英文摘要: (AP-1) DNA binding activity, suggesting the central rolesof these signaling cascades. Interestingly, CCY1a alsoeffectively blocked serum-induced l B-α phosphoryla-tion, l B-α degradation and nuclear factor- B (NF- B)binding activity. Based on these observations, we exam-ined the effect of CCY1a on serum-mediated Ras activity,an upstream regulator of the above signaling events. Thedata demonstrated a marked inhibition of Ras activationby CCY1a. We conclude that CCY1a blocks cell prolifera-tion via inhibition of the upstream effector of Ras anddownstream events, including p42/44 MAPK activationand c-fos and c-jun mRNA expression, as well as NF- Band AP-1 DNA binding activities.Excessive proliferation of vascular smooth muscle cells(VSMC) in the intima is an important etiologic factor invascular proliferative disorders such as atherosclerosisand restenosis after balloon angioplasty. Therefore, con-trol of VSMC growth may be a suitable therapeutic inter-vention in vascular proliferative disorders. In the presentwork, we have studied the 2-benzyloxybenzaldehyde(CCY1a)-mediated antiproliferative effect and its mecha-nisms of action. CCY1a inhibited serum-induced VSMCproliferation in a concentration-dependent manner, asdemonstrated using [ H]thymidine incorporation andMTT assays; the IC values were calculated to be 7.0 x10 and 1.2 x 10 M, respectively. Furthermore, it alsosignificantly suppressed serum-induced progression ofthe cell cycle, as shown by flow cytometric analysis.CCY1a as well as PD98059 almost completely abolishedserum-induced activation of p42/44 mitogen-activatedprotein kinase (MAPK), the downstream effectors of c-fosand c-jun mRNA expression and activator protein-1
- 中文關鍵字: --
- 英文關鍵字: Benzyloxybenzaldehyde analogue, Proliferation, Vascular, Smooth muscle Cells, Ras