title: Synthesis, characterization, in vitro cytotoxicity and anticancer effects of ruthenium(II) complexes on BEL-7402 cells.
abstract: Four new ruthenium(II) polypyridyl complexes [Ru(dmb)2(DQTT)](ClO4)2 (1) (DQTT=12-(1,4-dihydroquinoxalin-6-yl)-4,5,9,14-tetraazabenzo[b]triphenylene, dmb=4,4'-dimethyl-2,2'-bipyridine), [Ru(bpy)2(DQTT)](ClO4)2 (2) (bpy=2,2'-bipyridine), [Ru(phen)2(DQTT)](ClO4)2 (3) (phen=1,10-phenanthroline) and [Ru(dmp)2(DQTT)](ClO4)2 (4) (dmp=2,9-dimethyl-1,10-phenanthroline) were synthesized and characterized by elemental analysis, ESI-MS, (1)H NMR and (13)C NMR. The cytotoxic activity in vitro of the complexes was evaluated against human BEL-7402, A549, HeLa, HepG-2 and MG-63 cancer cell lines by MTT (3-(4,5-dimethylthiazole)-2,5-diphenyltetrazolium bromide) method. The IC50 values of complexes 1-4 against BEL-7402 cells are 31.8 ± 1.0, 35.8 ± 1.6, 29.0 ± 0.8 and 25.0 ± 0.9 μM, respectively. The morphological apoptosis was investigated with AO/EB (acridine orange/ethidium bromide) and Hoechst 33258 staining methods. The DNA damage was assayed by comet assay. The inhibition of cell migration was evaluated by the wound healing assay. The levels of ROS (reactive oxygen species) and the changes of mitochondrial membrane potential were studied under fluorescent microscope. The percentages in the cells of apoptotic and necrotic cells and the cell cycle arrest were determined by flow cytometry. The expression of Bcl-2 family proteins was investigated by western blot analysis. The results show that the complexes induce BEL-7402 cells apoptosis through a ROS-mediated mitochondrial dysfunction pathway, which was accompanied by regulation of the expression of Bcl-2 family proteins.
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: Bing-Jie
authors.initials: BJ
authors.lastname: Han
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: 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
authors.initials: B
authors.lastname: Tang
authors.affiliation: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wan
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. Electronic address: lyjche@163.com.
authors.forename: Yun-Jun
authors.initials: YJ
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D002460:Cell Line; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D017975:Ruthenium Compounds / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D017975:Ruthenium Compounds
keywords: Cytotoxicity in vitro; Mitochondrial membrane potential; Reactive oxygen species; Ruthenium(II) polypyridyl complexes; Western blot analysis