The aim of our study was to evaluate the in vitro and in vivo anti-proliferative potential of complex (2) [Cu (L1)Cl]Cl.2HO, where L1 = 1-[2-hydroxybenzyl(2-pyridylmethyl)amino]-3-(1-naphthyloxy)-2-propanol on lung carcinoma cell NCI-H460. Cell viability assay determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) colorimetric assay demonstrated that the complex (2) exhibits higher activity against the NCI-H460 cell, with an IC value lower than cisplatin (26.5 μM ± 1.1 and 203 ± 1.2 μM respectively). Cell death by apoptosis was investigated by flow cytometer analysis of sub-G1 populations in the cell cycle and Annexin V/Propidium Iodide assay. Changes on the cell surface and ultrastructure were detected by scanning and transmission electron microscopy. Our work revealed that complex (2) induced changes associated with apoptosis, such as plasma membrane blebbing and a lower microvilli amount, fragmentation and condensation of chromatin, alterations in mitochondria, and enlargement of the endoplasmic reticulum. Mitochondrial function of NCI-H460 cells evaluated by 5,5',6,6'-tetrachloro 1,1',3,3' tetraethylbenzimidazolylcarbocyanine iodide (JC-1) probes showed high loss of mitochondrial membrane potential when treated with complex (2). Moreover, caspase-12 measurement showed an expressive activation level, which is related to endoplasmic reticulum stress. In vivo assay using the murine model of human lung cancer cell showed that complex (2) and cisplatin has similar antineoplastic activity.
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