Induction of apoptosis in leukemia cell lines by new copper(II) complexes containing naphthyl groups via interaction with death receptors

Abstract

The synthesis, physico-chemical characterization and cytotoxicity of four new ligands and their respective copper(II) complexes toward two human leukemia cell lines (THP-1 and U937) are reported (i.e. [(HL1)Cu(μ-Cl)2Cu(HL1)]Cl2·H2O (1), [(H2L2)Cu(μ-Cl)2Cu(H2L2)]Cl2·5H2O (2), [(HL3)Cu(μ-Cl)2Cu(HL3)]Cl2·4H2O (3), [(H2L4)Cu(μ-Cl)2Cu(H2L4)]Cl2·6H2O (4)). Ligands HL1 and HL3 contain two pyridines, amine and alcohol moieties with a naphthyl pendant unit yielding a N3O coordination metal environment. Ligands H2L2 and H2L4 have pyridine, phenol, amine and alcohol groups with a naphthyl pendant unit providing a N2O2 coordination metal environment. These compounds are likely to be dinuclear in the solid state but form mononuclear species in solution. The complexes have an antiproliferative effect against both leukemia cell lines; complex (2) exhibits higher activity than cisplatin against U937 (8.20 vs 16.25μmoldm(-3)) and a comparable one against THP-1. These human neoplastic cells are also more susceptible than peripheral blood mononuclear cells (PBMCs) toward the tested compounds. Using C57BL/6 mice an LD50 of 55mgkg(-1) was determined for complex (2), suggesting that this compound is almost four times less toxic than cisplatin (LD50=14.5mgkg(-1)). The mechanism of cell death promoted by ligand H2L2 and by complexes (2) and (4) was investigated by a range of techniques demonstrating that the apoptosis signal triggered at least by complex (2) starts from an extrinsic pathway involving the activation of caspases 4 and 8. This signal is amplified by mitochondria with the concomitant release of cytochrome c and the activation of caspase 9.

A healable, recyclable and thermochromic epoxy resin for thermally responsive smart windows

“…S18 and S19†). Based on the above discussion and the literature reported by other research groups, 18,27,28,47–50 we can draw a conclusion that the sample is bright blue due to the presence of six-coordinated octahedral Ni 2+ ions, as both hydroxyl and imidazole form coordination bonds with Ni 2+ ions. When the temperature rises, the hydroxyl group with a weaker coordination ability has undergone coordination dissociation, while the coordination bond formed with the imidazole is weakened but still remains.…”

Novel copper(II) complexes with hydrazides and heterocyclic bases: Synthesis, structure and biological studies

“…5). Several copper(II) complexes were reported in literature by induce apoptosis, a form of programmed cell death that occurs in tumor cells as response to some anticancer agents [52][53][54].…”

In Vitro and In Vivo Relevant Antineoplastic Activity of Platinum(II) Complexes toward Triple-Negative MDA-MB-231 Breast Cancer Cell Line

“…Our group has been evaluating the cytotoxic activities of a series of coordination compounds containing different metal ions both in vitro and in vivo [ 20 , 21 , 22 , 23 , 24 ]. We previously showed the synthesis, characterization, and cytotoxic activity of four complexes containing platinum(II) as a metallic coordinating center ( Scheme 1 ), where treatment against U937 cell line with complex ( 3 ) [Pt(HL3)Cl]·H 2 O could induce the activation of both intrinsic and extrinsic apoptotic cascades, as well as perturbations in cell cycle and dysfunction of mitochondrial membrane potential [ 24 ].…”