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Studies of the anticancer activities of ruthenium(II) polypyridyl complexes toward human hepatocellular carcinoma BEL-7402 cells
Transition Metal Chemistry ( IF 1.6 ) Pub Date : 2019-06-10 , DOI: 10.1007/s11243-019-00315-5
Zhen-Hua Liang , Ya-Ning Wang , Zhi-Wei Xiong , Xiao-Yan Chen , Lin Tong

Two ruthenium(II) polypyridyl complexes formulated as [Ru(bpy)2(THPDP)](PF6)2 (1) and [Ru(ttbpy)2(THPDP)](PF6)2 (ttbpy = 4,4ʹ-ditertiary butyl-2,2ʹ-bipyridine) (2) were synthesized and characterized by elemental analysis, 1H NMR, 13C NMR and UV–Vis spectra. The cytotoxic activities of the complexes against cancer cell lines BEL-7402, A549, SGC-7901, HeLa and normal NIH3T3 cells were investigated by 3-(4,5-dimethylthiazole)-2,5-diphenyltetrazolium bromide (MTT) methods. The complexes show moderate cytotoxicity toward BEL-7402 and HeLa cells. The changes in mitochondrial membrane potential, intracellular Ca2+ and reactive oxygen species were studied by fluorescence microscopy. Both complexes can increase intracellular Ca2+ concentrations and ROS levels and induce a decrease in mitochondrial membrane potential. They also inhibit cell invasion and suppress cell proliferation at the G0/G1 phase. Additionally, they activate caspase 3, cleave PARP and regulate the expression of Bcl-2 family proteins. In short, the complexes induce apoptosis in BEL-7402 cells through a ROS-mediated mitochondria dysfunction pathway.

中文翻译:

钌(II)多吡啶配合物对人肝细胞癌BEL-7402细胞抗癌活性的研究

两种钌 (II) 多吡啶配合物配制成 [Ru(bpy)2(THPDP)](PF6)2 (1) 和 [Ru(ttbpy)2(THPDP)](PF6)2 (ttbpy = 4,4ʹ-二叔丁基) -2,2ʹ-联吡啶) (2) 被合成并通过元素分析、1H NMR、13C NMR 和UV-Vis 光谱表征。通过 3-(4,5-二甲基噻唑)-2,5-二苯基溴化四唑 (MTT) 方法研究了复合物对癌细胞系 BEL-7402、A549、SGC-7901、HeLa 和正常 NIH3T3 细胞的细胞毒活性。该复合物对 BEL-7402 和 HeLa 细胞显示出中等的细胞毒性。通过荧光显微镜研究线粒体膜电位、细胞内Ca2+和活性氧的变化。两种复合物都可以增加细胞内 Ca2+ 浓度和 ROS 水平,并诱导线粒体膜电位降低。它们还在 G0/G1 期抑制细胞侵袭并抑制细胞增殖。此外,它们激活 caspase 3,切割 PARP 并调节 Bcl-2 家族蛋白的表达。简而言之,复合物通过 ROS 介导的线粒体功能障碍途径诱导 BEL-7402 细胞凋亡。
更新日期:2019-06-10
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