title: Cytotoxicity, apoptosis, cell cycle arrest, reactive oxygen species, mitochondrial membrane potential, and Western blotting analysis of ruthenium(II) complexes.
abstract: Three new ruthenium(II) complexes-[Ru(bpy)2(adppz)](ClO4)2, [Ru(dmb)2(adppz)](ClO4)2, and [Ru(dmp)2(adppz)](ClO4)2 (bpy is 2,2'-bipyridine, adppz is 7-aminodipyrido[3,2-a:2',3'-c]phenazine, dmb is 4,4'-dimethyl-2,2'-bipyridine, and dmp is 2,9-dimethyl-1,10-phenanthroline)-were synthesized. [Ru(dmp)2(adppz)](ClO4)2 exhibits higher cytotoxicity than cisplatin toward A549, MG-63, and SKBR-3 cells. The apoptosis and cellular uptake were studied by fluorescence microscopy. [Ru(dmp)2(adppz)](ClO4)2 enhances the level of reactive oxygen species (ROS) and decreases the mitochondrial membrane potential. These complexes induce cell cycle arrest in S phase in BEL-7402 cells, and inhibit the antiproliferation of SKBR-3 cells at G0/G1 phase. Western blotting analysis shows that [Ru(dmp)2(adppz)](ClO4)2 induces apoptosis in BEL-7402 cells through activation of caspase 3, caspase 7, and procaspase 7 and ROS-mediated mitochondrial dysfunction pathways.
authors.affiliation: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, People's Republic of China.
authors.forename: Gan-Jian
authors.initials: GJ
authors.lastname: Lin
authors.forename: Guang-Bin
authors.initials: GB
authors.lastname: Jiang
authors.forename: Yang-Yin
authors.initials: YY
authors.lastname: Xie
authors.forename: Hong-Liang
authors.initials: HL
authors.lastname: Huang
authors.forename: Zhen-Hua
authors.initials: ZH
authors.lastname: Liang
authors.forename: Yun-Jun
authors.initials: YJ
authors.lastname: Liu
mesh_terms: D015082:2,2'-Dipyridyl / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009369:Neoplasms / Q000188:drug therapy; D010618:Phenanthrolines / Q000737:chemistry / Q000494:pharmacology; D010619:Phenazines / Q000737:chemistry / Q000494:pharmacology; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012428:Ruthenium / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: C560551:4,4'-dimethyl-2,2'-bipyridine; D000970:Antineoplastic Agents; D056831:Coordination Complexes; D010618:Phenanthrolines; D010619:Phenazines; D011725:Pyridines; D017382:Reactive Oxygen Species; D015082:2,2'-Dipyridyl; D012428:Ruthenium; C025205:1,10-phenanthroline