title: A novel copper complex of salicylaldehyde pyrazole hydrazone induces apoptosis through up-regulating integrin beta4 in H322 lung carcinoma cells.
abstract: 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.
authors.affiliation: Institute of Developmental Biology, School of Life Science, Shandong University, 27 Shanda South Road, Jinan 250100, China.
authors.forename: Chuandong
authors.initials: C
authors.lastname: Fan
authors.forename: Hua
authors.initials: H
authors.lastname: Su
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Baoxiang
authors.initials: B
authors.lastname: Zhao
authors.forename: Shangli
authors.initials: S
authors.lastname: Zhang
authors.forename: Junying
authors.initials: J
authors.lastname: Miao
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003300:Copper / Q000737:chemistry*; D005455:Fluorescent Antibody Technique; D006801:Humans; D006835:Hydrazones / Q000737:chemistry / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D039663:Integrin beta4 / Q000378:metabolism*; D008175:Lung Neoplasms / Q000473:pathology*; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology*; D034622:RNA Interference; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D006835:Hydrazones; D039663:Integrin beta4; D009942:Organometallic Compounds; D003300:Copper