High anticancer activity and apoptosis- and autophagy-inducing properties of novel lanthanide(III) complexes bearing 8-hydroxyquinoline-N-oxide and 1,10-phenanthroline
High anticancer activity and apoptosis- and autophagy-inducing properties of novel lanthanide(III) complexes bearing 8-hydroxyquinoline-N-oxide and 1,10-phenanthroline
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含有 8-羟基喹啉-N-氧化物和 1,10-菲咯啉的新型镧系元素 (III) 配合物具有高抗癌活性以及细胞凋亡和自噬诱导特性
DOI：
10.1039/d1dt00450f
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发表时间：
2021-03-26
影响因子：
4
通讯作者：
Liang, Hong
中科院分区：
文献类型：
--
作者：
Yang, Yan;Zhou, Zhen;Liang, Hong
在寻求具有增强的癌症化疗性质的稀土金属络合物的过程中，发现了七种带有8-羟基喹啉-N-氧化物（NQ）和1，10-菲咯啉（phen）配体的镧系元素（III）络合物，即，[Sm-III（NQ）（phen）（H2O）Cl-2]（Ln1）、[Eu-II（NQ）（phen）（H2O）Cl-2]（Ln2）、[Gd-III（NQ）（phen）（H2O）Cl-2]（Ln3）、[Dy-III（NQ）（phen）（H2O）Cl-2]（Ln4）、[Ho-III（NQ）（phen）（H2O）Cl-2]（Ln5）、[Er-III（NQ）（phen）（H2O）Cl-2]（Ln6），和[Yb-III（NQ）（phen）（H2O）Cl-2]（Ln 7）作为潜在的抗癌药物。配合物Ln 1-Ln 7对顺铂耐药的A549/DDP细胞表现出高的抗增殖活性（IC 50 = 0.025 - 0.097 μ M），而对正常HL-7702细胞表现出低毒性。此外，复合物Ln 1，并在较小程度上Ln 7，可以上调LC 3和Beclin 1的表达，下调p62，诱导顺铂耐药的A549/DDP细胞系的凋亡，这与Ln 1和Ln 7的细胞自噬诱导特性有关。此外，体内试验表明，Ln 1显着抑制A549/DDP异种移植肿瘤生长（56.5%）。这些结果表明，镧系元素（III）配合物Ln 1是一个有前途的候选人作为抗癌药物对顺铂耐药的A549/DDP细胞。
In the quest for rare earth metal complexes with enhanced cancer chemotherapeutic properties, the discovery of seven lanthanide(III) complexes bearing 8-hydroxyquinoline-N-oxide (NQ) and 1,10-phenanthroline (phen) ligands, i.e., [Sm-III(NQ)(phen)(H2O)Cl-2] (Ln1), [Eu-II(NQ)(phen)(H2O)Cl-2] (Ln2), [Gd-III(NQ)(phen)(H2O)Cl-2] (Ln3), [Dy-III(NQ)(phen)(H2O)Cl-2] (Ln4), [Ho-III(NQ)(phen)(H2O)Cl-2] (Ln5), [Er-III(NQ)(phen) (H2O)Cl-2] (Ln6), and [Yb-III(NQ)(phen)(H2O)Cl-2] (Ln7), as potential anticancer drugs is described. Complexes Ln1-Ln7 exhibit high antiproliferative activity against cisplatin-resistant A549/DDP cells (IC50 = 0.025-0.097 mu M) and low toxicity to normal HL-7702 cells. Moreover, complex Ln1, and to a lesser extent Ln7, can upregulate the expression of LC3 and Beclin1 and downregulate p62 to induce apoptosis in cisplatin-resistant A549/DDP cell lines, which is related to the cell autophagy-inducing properties of Ln1 and Ln7. Furthermore, in vivo assays suggest that Ln1 significantly inhibits A549/DDP xenograft tumor growth (56.5%). These results indicate that lanthanide(III) complex Ln1 is a promising candidate as an anticancer drug against cisplatin-resistant A549/DDP cells.