کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1316893 | 1499430 | 2016 | 11 صفحه PDF | دانلود رایگان |
• Four new ruthenium(II) complexes were synthesized and characterized.
• The cytotoxicity of the complexes against five cancer cell lines was investigated.
• The apoptosis, comet assay, cell migration and cellular uptake were investigated.
• The cell cycle arrest was investigated by flow cytometry.
• The expression of Bcl-2 family proteins was assayed by western blot analysis.
Four new ruthenium(II) polypyridyl complexes [Ru(dmb)2(DQTT)](ClO4)2 (1) (DQTT = 12-(1,4-dihydroquinoxalin-6-yl)-4,5,9,14-tetraazabenzo[b]triphenylene, dmb = 4,4′-dimethyl-2,2′-bipyridine), [Ru(bpy)2(DQTT)](ClO4)2 (2) (bpy = 2,2′-bipyridine), [Ru(phen)2(DQTT)](ClO4)2 (3) (phen = 1,10-phenanthroline) and [Ru(dmp)2(DQTT)](ClO4)2 (4) (dmp = 2,9-dimethyl-1,10-phenanthroline) were synthesized and characterized by elemental analysis, ESI-MS, 1H NMR and 13C NMR. The cytotoxic activity in vitro of the complexes was evaluated against human BEL-7402, A549, HeLa, HepG-2 and MG-63 cancer cell lines by MTT (3-(4,5-dimethylthiazole)-2,5-diphenyltetrazolium bromide) method. The IC50 values of complexes 1–4 against BEL-7402 cells are 31.8 ± 1.0, 35.8 ± 1.6, 29.0 ± 0.8 and 25.0 ± 0.9 μM, respectively. The morphological apoptosis was investigated with AO/EB (acridine orange/ethidium bromide) and Hoechst 33258 staining methods. The DNA damage was assayed by comet assay. The inhibition of cell migration was evaluated by the wound healing assay. The levels of ROS (reactive oxygen species) and the changes of mitochondrial membrane potential were studied under fluorescent microscope. The percentages in the cells of apoptotic and necrotic cells and the cell cycle arrest were determined by flow cytometry. The expression of Bcl-2 family proteins was investigated by western blot analysis. The results show that the complexes induce BEL-7402 cells apoptosis through a ROS-mediated mitochondrial dysfunction pathway, which was accompanied by regulation of the expression of Bcl-2 family proteins.
Four new Ru(II) complexes [Ru(N-N)2(DQTT)](ClO4)2 were synthesized and characterized. The cytotoxicity, apoptosis, cell migration, cell cycle arrest and expression of proteins were investigated.Figure optionsDownload as PowerPoint slide
Journal: Journal of Inorganic Biochemistry - Volume 157, April 2016, Pages 62–72