A novel copper complex of salicylaldehyde pyrazole hydrazone induces apoptosis through up-regulating integrin β4 in H322 lung carcinoma cells
A novel copper complex of salicylaldehyde pyrazole hydrazone induces apoptosis through up-regulating integrin β4 in H322 lung carcinoma cells
复制标题
DOI：
10.1016/j.ejmech.2009.12.048
复制
发表时间：
2010-04-01
影响因子：
6.7
通讯作者：
Miao, JunYing
中科院分区：
文献类型：
--
作者：
Fan, ChuanDong;Su, Hua;Miao, JunYing
鉴于一些已报道的铜配合物的抗癌活性增强，以及我们先前发现的9个新的抗增殖水杨醛吡唑肼(SPH)衍生物，我们制备了这些SPH衍生物的铜配合物(CuSPHs)，通过诱导细胞凋亡，这些铜配合物对A549细胞的生长抑制作用比相应的SPHs更强。其中，(E)-N‘-(2-hydroxybenzylidene)-1-(4-tert-butylbenzy1)-3-phenyl-1H-pyrazole-5-carbohydrazide，的铜络合物Cu-16在选择性和药效方面表现出明显的优势。免疫荧光和Western印迹分析显示，经铜-16处理的H322细胞整合素β4蛋白水平升高，整合素β4基因敲除可显著抑制铜-16诱导的H322细胞的凋亡。综上所述，这些结果表明，铜-16通过上调整合素β4的蛋白水平促进H322细胞的凋亡。(C)2009年爱思唯尔·马森SAS。版权所有。
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-butylbenzy1)-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 beta 4 upon Cu-16 treatment, and knockdown of integrin beta 4 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 beta 4. (C) 2009 Elsevier Masson SAS. All rights reserved.