title: The induction of apoptosis in HepG-2 cells by ruthenium(II) complexes through an intrinsic ROS-mediated mitochondrial dysfunction pathway.
abstract: Four new ruthenium(II) polypyridyl complexes [Ru(N-N)2(dhbn)](ClO4)2 (N-N = dmb: 4,4'-dimethyl-2,2'-bipyridine 1; bpy = 2,2'-bipyridine 2; phen = 1,10-phenanthroline 3; dmp = 2,9-dimethyl-1,10-phenanthroline 4) were synthesized and characterized. The cytotoxicity in vitro of the ligand and complexes toward HepG-2, HeLa, MG-63 and A549 were assayed by MTT method. The IC50 values of the complexes against the above cells range from 17.7 ± 1.1 to 45.1 ± 2.8 μM. The cytotoxic activity of the complexes against HepG-2 cells follows the order of 4 > 2 > 3 > 1. Ligand shows no cytotoxic activity against the selected cell lines. Cellular uptake, apoptosis, comet assay, reactive oxygen species, mitochondrial membrane potential, cell cycle arrest, and the expression of proteins involved in apoptosis pathway induced by the complexes were investigated. The results indicate that complexes 1-4 induce apoptosis in HepG-2 cells through an intrinsic ROS-mediated mitochondrial dysfunction pathway.
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.
authors.forename: Shang-Hai
authors.initials: SH
authors.lastname: Lai
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: Cheng
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Microbiology and Immunology, Guangdong Pharmaceutical University, Guangzhou, 510006, PR China. Electronic address: Huiyin0103@163.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Yin
authors.affiliation: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
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. Electronic address: lyjche@163.com.
authors.forename: Yun-Jun
authors.initials: YJ
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001692:Biological Transport; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D009942:Organometallic Compounds / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D010618:Phenanthrolines / Q000737:chemistry; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012428:Ruthenium / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D010618:Phenanthrolines; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D012428:Ruthenium; D053148:Caspase 3; D053179:Caspase 7; C025205:1,10-phenanthroline
keywords: Cell cycle arrest; Comet assay; Cytotoxicity in vitro; Ruthenium(II) polypyridyl complex; Western blot analysis