Biometals ( IF 3.5 ) Pub Date : 2021-04-04 , DOI: 10.1007/s10534-021-00302-3 Wagner da S Terra 1, 2 , Érika S Bull 1, 2 , Samila R Morcelli 1, 3 , Rafaela R Moreira 1, 4 , Leide Laura F Maciel 5 , João Carlos de A Almeida 5 , Milton M Kanashiro 6 , Christiane Fernandes 1, 7 , Adolfo Horn 1, 7
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 N2O2 donor sets. The complex containing homopiperazine unit presented the best antiproliferative effect and selectivity against lung cancer cell line NCI-H460, showing inhibitory concentration (IC50) 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.
中文翻译:
水溶性铜 (II) 配合物通过凋亡细胞死亡途径的抗肿瘤活性:二氨基单元对肺癌 NCI-H460 细胞系选择性的影响
三种水溶性铜 (II) 配位化合物含有配体 3,3'-(ethane-1, 2-diylbis(azanediyl))dipropanamide (BCEN)、3,3'-(piperazine-1,4-diyl)dipropanamide (BPAP) 或 3,3'-and (1,4-diazepane-1,4-diyl)在这项工作中报道了二丙酰胺(BPAH)。配体包含不同的二胺单元(乙二胺、哌嗪或高哌嗪)和连接到二胺中心的两个丙酰胺单元,产生 N 2 O 2供体组。含有高哌嗪单元的复合物对肺癌细胞株NCI-H460的抗增殖作用和选择性最好,抑制浓度(IC 50 )为58 μmol dm -3和选择性指数 (SI) > 3.4。通过 Sub-G1 细胞群分析和膜联蛋白 V 和碘化丙啶 (PI) 标记技术研究了该复合物促进细胞死亡的机制,表明该复合物通过细胞凋亡促进死亡。透射电子显微镜研究与线粒体膜电位分析的结果一致,并且还显示了其他细胞器的损伤,包括内质网。