A novel copper complex of salicylaldehyde pyrazole hydrazone induces apoptosis through up-regulating integrin beta4 in H322 lung carcinoma cells.
Fan C, Su H, Zhao J, Zhao B, Zhang S, Miao J.
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.