title: Protein binding and anticancer activity studies of ruthenium(II) polypyridyl complexes toward BEL-7402 cells.
abstract: Four new ruthenium(II) polypyridyl complexes [Ru(dmb)2(dqtbt)](ClO4)2 (1) (dqtbt=12-(2,3-diphenyl-quinoxalin-6-yl)-4,5,10,13-tetraazabenzo[b]triphenylene, dmb=4,4'-dimethyl-2,2'-bipyridine), [Ru(bpy)2(dqtbt)](ClO4)2 (2) (bpy=2,2'-bipyridine), [Ru(phen)2(dqtbt)](ClO4)2 (3) (phen=1,10-phenanthroline) and [Ru(dmp)2(dqtbt)](ClO4)2 (4) (dmp=2,9-dimethyl-1,10-phenanthroline) were synthesized and characterized. The cytotoxicity in vitro of the complexes was evaluated against human BEL-7402, A549, HeLa, HepG-2 and MG-63 cancer cell lines. These complexes are sensitive to BEL-7402 cells, the IC50 values are 4.9±0.5, 4.6±0.4, 7.7±1.8 and 1.9±0.3μM toward BEL-7402 cells. The complexes can increase the levels of reactive oxygen species and induce the decrease of mitochondrial membrane potential. Morphological and comet assay studies show that the complexes can effectively induce apoptosis in BEL-7402 cells. Complexes 1-4 inhibit the cell growth at G0/G1 phase in BEL-7402 cell line. The complexes can downregulate the expression of Bcl-2 and Bcl-x proteins and upregulate the levels of Bid protein in BEL-7402 cells. The results show that the complexes induce BEL-7402 cell apoptosis through a ROS-mediated mitochondrial dysfunction pathway. In addition, the complexes show strong protein-binding affinities.
authors.affiliation: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China.
authors.forename: Shang-Hai
authors.initials: SH
authors.lastname: Lai
authors.affiliation: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Instrumentation Analysis and Research Center, Sun Yat-Sen University, Guangzhou 510275, PR China.
authors.forename: Jun-Hua
authors.initials: JH
authors.lastname: Yao
authors.affiliation: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China.
authors.forename: Bing-Jie
authors.initials: BJ
authors.lastname: Han
authors.affiliation: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China.
authors.forename: Guang-Bin
authors.initials: GB
authors.lastname: Jiang
authors.affiliation: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China.
authors.forename: Chuan-Chuan
authors.initials: CC
authors.lastname: Zeng
authors.affiliation: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China. Electronic address: lyjche@163.com.
authors.forename: Yun-Jun
authors.initials: YJ
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004249:DNA Damage; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D011485:Protein Binding; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011725:Pyridines / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism; D017975:Ruthenium Compounds / Q000737:chemistry / Q000494:pharmacology*; D013057:Spectrum Analysis / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D011725:Pyridines; D017382:Reactive Oxygen Species; D017975:Ruthenium Compounds; D020169:Caspases
keywords: Cytotoxicity in vitro; Mitochondrial membrane potential; Reactive oxygen species; Ru (II) polypyridyl complexes; Western blot analysis