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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
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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
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Journal Article
Copper(II) complexes with naringenin and hesperetin: cytotoxic activity against A 549 human lung adenocarcinoma cells and investigation on the mode of action
2016
Overview
Copper(II) complexes
[Cu(H
2
O)
2
(L1)(phen)](ClO
4
)
(
1
) and
[Cu(H
2
O)(L2)(phen)](ClO
4
)
(
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 IC
50
= 16.42 µM (
1
) and IC
50
= 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.
Graphical abstract
Publisher
Springer Netherlands,Springer Nature B.V
Subject
/ Adenocarcinoma - drug therapy
/ Antineoplastic Agents - administration & dosage
/ Antineoplastic Agents - chemistry
/ Binding
/ Biomedical and Life Sciences
/ Coordination Complexes - administration & dosage
/ Coordination Complexes - chemistry
/ Copper
/ Copper - administration & dosage
/ Flavanones - administration & dosage
/ Hesperidin - administration & dosage
/ Human
/ Human Umbilical Vein Endothelial Cells - drug effects
/ Humans
/ Ligands
/ Lung Neoplasms - drug therapy
/ Lungs
/ Tumors
/ Veins
