Institute of Developmental Biology, School of Life Science, Shandong University, 27 Shanda South Road, Jinan 250100, China.
Eur J Med Chem. 2010 Apr;45(4):1438-46. doi: 10.1016/j.ejmech.2009.12.048. Epub 2010 Jan 4.
In light of the increased anticancer activities of some reported copper complexes and our previous finding of nine novel anti-proliferative salicylaldehyde pyrazole hydrazone (SPH) derivatives, we prepared copper complexes of these SPH derivatives (Cu-SPHs), which turned out to be stronger growth inhibitors to A549 cells than their corresponding SPHs via inducing apoptosis. Among them, the copper complex of (E)-N'-(2-hydroxybenzylidene)-1-(4-tert-butylbenzyl)-3-phenyl-1H-pyrazole-5-carbohydrazide, termed Cu-16, exhibited an advantage in selectivity and efficacy over the others. Immunofluorescence and Western blot analyses showed an elevated protein level of integrin beta4 upon Cu-16 treatment, and knockdown of integrin beta4 significantly inhibited Cu-16 induced apoptosis in H322 cells. Taken together, the results indicate that Cu-16 promotes apoptosis in H322 cells through elevating the protein level of integrin beta4.
鉴于一些报道的铜配合物的抗癌活性增加，以及我们之前发现的九种新型具有抗增殖作用的水杨醛吡唑腙（SPH）衍生物，我们制备了这些 SPH 衍生物的铜配合物（Cu-SPH），结果表明，通过诱导细胞凋亡，它们对 A549 细胞的生长抑制作用强于相应的 SPH。其中，（E）-N'-(2-羟基苄叉基）-1-(4-叔丁基苄基）-3-苯基-1H-吡唑-5-甲酰肼的铜配合物，称为 Cu-16，在选择性和功效方面优于其他配合物。免疫荧光和 Western blot 分析表明，Cu-16 处理后整合素β4的蛋白水平升高，而整合素β4 的敲低显著抑制了 H322 细胞中 Cu-16 诱导的细胞凋亡。总之，这些结果表明，Cu-16 通过提高整合素β4 的蛋白水平促进 H322 细胞凋亡。
