The induction of mitochondria-mediated apoptosis in cancer cells by ruthenium(ii) asymmetric complexes

• Published in: Metallomics 2013-06, Vol.5 (7), p.844-854
• Main Authors: Qian, Chen, Wang, Jin-Quan, Song, Cui-Lan, Wang, Li-Li, Ji, Liang-Nian, Chao, Hui
• Format: Article
• Language: English
• Subjects: Apoptosis - drug effects; Apoptosis - physiology; Cell Cycle - drug effects; Cell Line, Tumor; Humans; Membrane Potential, Mitochondrial - drug effects; Mitochondria - drug effects; Mitochondria - physiology; Reactive Oxygen Species - metabolism; Ruthenium Compounds - pharmacology
• ISSN: 1756-5901; 1756-591X
• DOI: 10.1039/c3mt20270d

Four ruthenium( ii ) asymmetric complexes, [Ru(bpy) 2 (PAIDH)] 2+ (bpy = 2,2-bipyridine, PAIDH = 2-pyridyl-1 H -anthra[1,2-d]imidazole-6,11-dione, 1 ), [Ru(phen) 2 (PAIDH)] 2+ (phen = 1,10-phenanthroline, 2 ), [Ru(dmp) 2 (PAIDH)] 2+ (dmp = 4,7-dimethyl-1,10-phenanthroline, 3 ) and [Ru(dip) 2 (PAIDH)] 2+ (dip = 4,7-diphenyl-1,10-phenanthroline, 4 ), 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 4 , accounting for the greatest cellular uptake. Complex 4 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 4 induced cancer cell apoptosis by acting on mitochondrial pathways. Four ruthenium( ii ) asymmetric complexes were found to possess potent cellular uptake properties and induce HeLa cell apoptosis by acting on mitochondrial pathways.