title: The induction of mitochondria-mediated apoptosis in cancer cells by ruthenium(II) asymmetric complexes.
abstract: Four ruthenium(ii) asymmetric complexes, [Ru(bpy)2(PAIDH)](2+) (bpy = 2,2'-bipyridine, PAIDH = 2-pyridyl-1H-anthra[1,2-d]imidazole-6,11-dione, ), [Ru(phen)2(PAIDH)](2+) (phen = 1,10-phenanthroline, ), [Ru(dmp)2(PAIDH)](2+) (dmp = 4,7-dimethyl-1,10-phenanthroline, ) and [Ru(dip)2(PAIDH)](2+) (dip = 4,7-diphenyl-1,10-phenanthroline, ), have been synthesized and characterized. These complexes displayed potent anti-proliferation activity against various cancer cell lines and had high selectivity between tumor cells and normal cells. HeLa cells exhibited the highest sensitivity to complex , accounting for the greatest cellular uptake. Complex was shown to accumulate preferentially in the mitochondria of HeLa cells and induced apoptosis via the mitochondrial pathway, which involved ROS generation, mitochondrial membrane potential depolarisation, and Bcl-2 and caspase family members activation. These results demonstrated that complex induced cancer cell apoptosis by acting on mitochondrial pathways.
authors.affiliation: MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, State Key Laboratory of Optoelectronic Materials and Technologies, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou, P. R. China.
authors.forename: Chen
authors.initials: C
authors.lastname: Qian
authors.forename: Jin-Quan
authors.initials: JQ
authors.lastname: Wang
authors.forename: Cui-Lan
authors.initials: CL
authors.lastname: Song
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Wang
authors.forename: Liang-Nian
authors.initials: LN
authors.lastname: Ji
authors.forename: Hui
authors.initials: H
authors.lastname: Chao
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D017975:Ruthenium Compounds / Q000494:pharmacology*
chemical_list: D017382:Reactive Oxygen Species; D017975:Ruthenium Compounds