In vitro apoptosis-inducing effect and gene expression profiles of mixed ligand Cu(ii) complexes derived from 4-acyl pyrazolones on human lung cancer cells

Abstract

In order to study the less understood anti-tumor mechanism of pyrazolone based mixed ligand complexes, four Cu(II) mixed ligand complexes [Cu(L1)(Phen)NO₃] (1), [Cu(L2)(Bipy)NO₃] (2), [Cu(L2)(Phen)NO₃] (3) and [Cu(L2)(Bipy)NO₃] (4) [L1 = 3-methyl-5-oxo-1-phenyl-4,5-dihydro-1H-pyrazole-4-carbaldehyde; L2 = 4-(1-naphthoyl)-3-methyl-1-(p-tolyl)-1H-pyrazol-5(4H)-one] have been synthesized and fully characterized. Single crystal X-ray diffraction analysis of three complexes indicated mononuclear structures exhibiting square pyramidal geometries. The inhibitory effects of the complexes on the cell population growth of the human lung carcinoma (A549) and human lung epithelial cell lines (L132) were determined by MTT assay, DAPI staining and DCFDA staining, which assessed mitochondrial dysfunction, nuclear condensation and intracellular oxidative stress, respectively. The expression levels of Bax (pro-apoptotic) and BCl2 (anti-apoptotic) genes were also studied in A549 cells wherein, both genes showed moderate downregulation after treatment with all the test complexes.