Abstract

--- - "The main goal of this work was to screen the antiproliferative activity and mechanism of actions of two copper complexes: [Cu(dmp)(2)(CH3CN)](2+) (1) and [Cu(phen)(2)(CH3CN)](2+) (2) on 2D and 3D colorectal cancer cells models. Cell viability studies on three colorectal cancer cell lines (HT-29, LS174T, Caco-2) displayed that 1 showed more robust antiproliferative activity than 2 and cisplatin. Intracellular copper content (63.24% and 48.06% for 1 and 2, respectively) can explain the differences in the cytotoxicity assay." - ROS production is the primary mechanism of action involved in the antiproliferative activity of 1 showing 4-, 70- and 2.5- fold increased values of ROS level for HT-29, LS174T, Caco-2 cancer cell lines, respectively. This effect takes place along with the depolarization of the mitochondrial membrane at 2 mu M. Besides, both complexes increased apoptosis on three cancer cell lines at low micromolar concentrations (0.5-2.5 mu M). Moreover, 1 and 2 inhibited NF-kappa B pathway both in HT-29-NF-kappa B-hrGFP monolayer (0.5 to 1 mu M) and spheroids HT-29 GFP (5 to 10 mu M). This inhibitory effect leads to an inactivation of the MMP-9 expression on HT-29 cell line. - Altogether, these results showed that 1 exhibits antiproliferative activity on human colorectal cancer cells in the monolayer and the 3D model.