Novel Complex of Copper and a Salicylaldehyde Pyrazole Hydrazone Derivative Induces Apoptosis through Up-Regulating Integrin beta 4 in Vascular Endothelial Cells

作者：Fan Chuandong; Zhao Jing; Zhao Baoxiang^*; Zhang Shangli; Miao Junying

来源：Chemical Research in Toxicology, 2009, 22(9): 1517-1525.

DOI：10.1021/tx900111y

To determine apoptosis modulators of human umbilical vein endothelial cells (HUVECs), we prepared 9 novel complexes of copper (Cu) and salicylaldehyde pyrazole hydrazone (SPH) derivatives (Cu-SPHs). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay revealed that all of the SPHs and Cu-SPHs effectively inhibited cell growth. Six of the 9 CU-SPHs induced apoptosis ill HUVECs. Among the 9 Cu-SPHs, the complex of Cu and (E)-N'-(2-hydroxybenzylidene)-1-benzyl-3-phenyl- 1H-pyrazole-5-carbohydrazide, named Cu-15, was one of the most effective apoptosis inducers and inhibited angiogenesis on Matrigel and HUVEC migration in vitro. We further Studied the mechanism of Cu-15 action and found that the protein level of integrin beta 4 increased with 10 mu M Cu-15 treatment for 12 or 24 h. Knockdown of integrin P4 by RNA interference significantly inhibited apoptosis induced by Cu-15 ill HUVECs. Thus, high level of integrin P4 could promote apoptosis induced by Cu-15. Cu-15 might be a useful tool for further investigating the functions of integrin beta 4 in regulating angiogenesis and HUVEC apoptosis.

• 出版日期2009-9
• 单位山东大学