Ru(II) Complexes Bearing O, O-Chelated Ligands Induced Apoptosis in A549 Cells through the Mitochondrial Apoptotic Pathway
Ru(II) Complexes Bearing O, O-Chelated Ligands Induced Apoptosis in A549 Cells through the Mitochondrial Apoptotic Pathway
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带有 O, O-螯合配体的 Ru(II) 配合物通过线粒体凋亡途径诱导 A549 细胞凋亡
DOI：
10.1155/2020/8890950
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发表时间：
2020-08-17
影响因子：
3.8
通讯作者：
Chen, Lanmei
中科院分区：
文献类型：
--
作者：
Chen, Jincan;Wang, Jie;Chen, Lanmei
合成了两种新的含O，O螯合配体的Ru（II）配合物Ru（dip）2（SA）（Ru-1）和Ru（dmp）2（SA）（Ru-2）（dip = 4，7-二苯基-1，10-菲咯啉; dmp = 2，9-二甲基-1，10-菲咯啉; SA =水杨酸盐），并对其体外细胞毒性进行了评价。发现这些配合物对不同类型的人类癌症（包括A549（人类肺癌）、MCF-7（乳腺癌）、HeLa（人类宫颈癌）和HepG 2（人类肝细胞癌）细胞系）表现出中等的抗肿瘤活性，但与顺铂相比，对人类正常细胞系BEAS-2B（永生化人类支气管上皮细胞）表现出低毒性。进一步研究发现，这些复合物可诱导A549细胞凋亡，包括激活caspase家族蛋白和聚腺苷二磷酸核糖聚合酶（PARP），降低Bcl-2/Bax和Bcl-xl/Bad比值，增加细胞活性氧（ROS）积累，引发DNA损伤，降低线粒体膜电位（MMP），导致线粒体释放细胞色素c。值得注意的是，配合物Ru-1对发育中的斑马鱼胚胎显示出低毒性。所得结果表明，这些新的合成配合物有潜力开发为肺癌治疗的低毒性药物。
Two new Ru(II) complexes containing O, O-chelated ligands, Ru(dip)2(SA) (Ru-1) and Ru(dmp)2(SA) (Ru-2) (dip = 4,7-diphenyl-1,10-phenanthroline; dmp = 2,9-dimethyl-1,10-phenanthroline; SA = salicylate) were synthesized to evaluate their cytotoxicity in vitro. These complexes were found to exhibit moderate antitumor activity to different types of human cancers, including A549 (human lung carcinoma), MCF-7 (breast cancer), HeLa (human cervical cancer), and HepG2 (human hepatocellular carcinoma) cell lines, but displayed low toxicity to human normal cell lines BEAS-2B (immortalized human bronchial epithelial cells) when compared with that of cisplatin. Further studies revealed that these complexes could induce apoptosis in A549 cells, including activating caspase family proteins and poly (ADP-ribose) polymerase (PARP), reducing Bcl-2/Bax and Bcl-xl/Bad ratio, enhancing cellular reactive oxygen species (ROS) accumulation, triggering DNA damage, decreasing mitochondrial membrane potential (MMP), and leading cytochrome c release from mitochondria. Notably, complex Ru-1 showed low toxicity to developing zebrafish embryos. The obtained results suggest that these new synthetic complexes have the potential to be developed as low-toxicity agents for lung cancer treatment.