Antitumor activity via apoptotic cell death pathway of water soluble copper(II) complexes: effect of the diamino unit on selectivity against lung cancer NCI-H460 cell line

The cytotoxicity against five human tumor cell lines (THP-1, U937, Molt-4, Colo-205 and NCI-H460) of three water soluble copper(II) coordination compounds containing the ligands 3,3′-(ethane-1,2-diylbis(azanediyl))dipropanamide (BCEN), 3,3′-(piperazine-1,4-diyl)dipropanamide (BPAP) or 3,3′-and (1,4-diazepane-1,4-diyl)dipropanamide (BPAH) are reported in this work. The ligands contain different diamine units (ethylenediamine, piperazine or homopiperazine) and two propanamide units attached to the diamine centers, resulting in N 2 O 2 donor sets. The complex containing homopiperazine unit presented the best antiproliferative effect and selectivity against lung cancer cell line NCI-H460, showing inhibitory concentration (IC 50 ) of 58 μmol dm −3 and Selectivity Index (SI) > 3.4. The mechanism of cell death promoted by the complex was investigated by Sub-G1 cell population analysis and annexin V and propidium iodide (PI) labeling techniques, suggesting that the complex promotes death by apoptosis. Transmission electron microscopy investigations are in agreement with the results presented by mitochondrial membrane potential analysis and also show the impairment of other organelles, including endoplasmic reticulum.