Synthesis of ruthenium ( II ) complexes and investigation of their antiproliferative mechanism against osteosarcoma cells
INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE(2018)
摘要
The objective of this study was to synthesize Ruthenium(II) complexes and investigate their anti-proliferative mechanism against osteosarcoma cells. Three ruthenium(II) polypyridyl complexes [Ru(dmb)2(taptp)](ClO4)2 (1), [Ru(bpy)2(taptp)](ClO4)2 (2) and [Ru(phen)2(taptp)](ClO4)2 (3) were synthesized and characterized. The IC50 values of 1, 2 and 3 towards MG-63 cells were 7.1 ± 0.6, 6.4 ± 0.4 and 8.4 ± 0.6 μM. These cytotoxic activities of the complexes against MG-63 cells were comparable with cisplatin under the same conditions. The complexes could effectively inhibit cell migration, induce cell cycle arrest and induce apoptosis of MG-63 cells. The complexes could enter into the cytoplasm, accumulate in the cell nuclei and induce DNA fragmentation. ROS and mitochondrial membrane potential assays demonstrated that complexes 1, 2 and 3 could increase the levels of ROS and induce the decrease of mitochondrial membrane potential. Additionally, the complexes downregulated the expression of antiapoptotic protein Bcl-x and upregulated the expression of proapoptotic protein Bid. These data indicate that the Ruthenium(II) complexes induce apoptosis of MG-63 cells through a ROS-mediated mitochondrial dysfunction pathway, which is accompanied to regulate the expression of Bcl-2 family proteins.
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关键词
Ru(II) complexes, cytotoxicity in vitro, apoptosis, mitochondrial membrane potential, western blot analysis
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