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  • Copper(II) complexes with naringenin and hesperetin: cytotoxic activity against A 549 human lung adenocarcinoma cells and investigation on the mode of action.

Copper(II) complexes with naringenin and hesperetin: cytotoxic activity against A 549 human lung adenocarcinoma cells and investigation on the mode of action.

Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine (2015-11-20)
Lenka V Tamayo, Ligiane R Gouvea, Anna C Sousa, Ronniel M Albuquerque, Sarah Fernandes Teixeira, Ricardo Alexandre de Azevedo, Sonia R W Louro, Adilson Kleber Ferreira, Heloisa Beraldo
RESUMEN

Copper(II) complexes [Cu(H2O)2 (L1)(phen)](ClO4) (1) and [Cu(H2O)(L2)(phen)](ClO4) (2) (HL1 = naringenin; HL2 = hesperetin) were obtained, in which an anionic flavonoid ligand is attached to the metal center along with 1,10-phenanthroline (phen) as co-ligand. Complexes (1) and (2) were assayed for their cytotoxic activity against A549 lung carcinoma and against normal lung fibroblasts (LL-24) and human umbilical vein endothelial cells (HUVEC). We found IC50 = 16.42 µM (1) and IC50 = 5.82 µM (2) against A549 tumor cells. Complexes (1) and (2) exhibited slight specificity, being more cytotoxic against malignant than against non-malignant cells. 1 and 2 induced apoptosis on A549 cells in a mitochondria-independent pathway, and showed antioxidant activity. The antioxidant effect of the complexes could possibly improve their apoptotic action, most likely by a PI3K-independent reduction of autophagy. Complexes (1) and (2) interact in vitro with calf thymus DNA by an intercalative binding mode. EPR data indicated that 1 and 2 interact with human serum albumin (HSA) forming mixed ligand species.

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Sigma-Aldrich
TRAIL murine, recombinant, expressed in E. coli, ≥95% (SDS-PAGE)

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