Guangxi Key Lab of Agricultural Resources Chemistry and Biotechnology, College of Chemistry and Food Science, Yulin Normal University, 1303 Jiaoyudong Road, Yulin 537000, PR China.
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, P. R. China.
Dalton Trans. 2021 May 4;50(17):5828-5834. doi: 10.1039/d1dt00450f.
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., [SmIII(NQ)(phen)(H2O)Cl2] (Ln1), [EuII(NQ)(phen)(H2O)Cl2] (Ln2), [GdIII(NQ)(phen)(H2O)Cl2] (Ln3), [DyIII(NQ)(phen)(H2O)Cl2] (Ln4), [HoIII(NQ)(phen)(H2O)Cl2] (Ln5), [ErIII(NQ)(phen)(H2O)Cl2] (Ln6), and [YbIII(NQ)(phen)(H2O)Cl2] (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 μM) 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.
在探索具有增强癌症化学治疗特性的稀土金属配合物的过程中，我们发现了七种含有 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）配合物，即 [SmIII(NQ)(phen)(H2O)Cl2]（Ln1）、[EuII(NQ)(phen)(H2O)Cl2]（Ln2）、[GdIII(NQ)(phen)(H2O)Cl2]（Ln3）、[DyIII(NQ)(phen)(H2O)Cl2]（Ln4）、[HoIII(NQ)(phen)(H2O)Cl2]（Ln5）、[ErIII(NQ)(phen)(H2O)Cl2]（Ln6）和 [YbIII(NQ)(phen)(H2O)Cl2]（Ln7），它们被认为是有潜力的抗癌药物。配合物 Ln1-Ln7 对顺铂耐药的 A549/DDP 细胞具有高的抗增殖活性（IC50 = 0.025-0.097 μM），且对正常 HL-7702 细胞的毒性较低。此外，配合物 Ln1，在较小程度上还有 Ln7，可以上调 LC3 和 Beclin1 的表达，下调 p62 的表达，从而诱导顺铂耐药的 A549/DDP 细胞系发生凋亡，这与 Ln1 和 Ln7 诱导细胞自噬的特性有关。此外，体内实验表明，Ln1 显著抑制 A549/DDP 异种移植肿瘤的生长（56.5%）。这些结果表明，镧系元素（III）配合物 Ln1 是一种很有前途的针对顺铂耐药的 A549/DDP 细胞的抗癌药物候选物。
