A novel copper complex of salicylaldehyde pyrazole hydrazone induces apoptosis through up-regulating integrin β4 in H322 lung carcinoma cells

• DOI: 10.1016/j.ejmech.2009.12.048
• Publication Date: 2010-01-05T09:08:59Z
• Authors: ChuanDong Fan; Hua Su; Jing Zhao; BaoXiang Zhao; ShangLi Zhang; JunYing Miao
• Keywords: Salicylaldehyde; Pyrazole; Hydrazone

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.