title: Ruthenium(II) complexes: DNA-binding, cytotoxicity, apoptosis, cellular localization, cell cycle arrest, reactive oxygen species, mitochondrial membrane potential and western blot analysis.
abstract: The aim of our study was to investigate DNA-binding and cytotoxic activity of the four new Ru(II) polypyridyl complexes [Ru(dmb)₂(HMHPIP)](ClO₄)₂ (1), [Ru(bpy)₂(HMHPIP)](ClO₄)₂ (2), [Ru(phen)₂(HMHPIP)](ClO₄)₂ (3) and [Ru(dmp)₂(HMHPIP)](ClO₄)₂ (4). The complexes interact with DNA through intercalative mode and show relatively high cytotoxic activity against A549 cells, no cytotoxicity toward MG-63 cells. Complexes 1-4 can enhance the levels of ROS in A549 cells and induce the decrease of the mitochondrial membrane potential. These complexes inhibit the cell growth in A549 cells at G0/G1 or S phase. Complex 3 activated caspase 7, and down-regulated the expression of the anti-apoptotic protein Bcl-2. Complexes 1-4 induce apoptosis in A549 cells through ROS-mediated mitochondrial dysfunction pathway.
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: Guang-Bin
authors.initials: GB
authors.lastname: Jiang
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: Xiu-Zhen
authors.initials: XZ
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China.
authors.forename: Ji
authors.initials: J
authors.lastname: Wang
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: Yang-Yin
authors.initials: YY
authors.lastname: Xie
authors.affiliation: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China.
authors.forename: Gan-Jian
authors.initials: GJ
authors.lastname: Lin
authors.affiliation: School of Life Science and Biopharmaceutical, Guangdong Pharmaceutical University, Guangzhou 510006, PR China. Electronic address: hhongliang@163.com.
authors.forename: Hong-Liang
authors.initials: HL
authors.lastname: Huang
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: D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity*; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D053837:DNA Cleavage / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D007364:Intercalating Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012428:Ruthenium / Q000737:chemistry*; D014466:Ultraviolet Rays
chemical_list: D056831:Coordination Complexes; D007364:Intercalating Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D012428:Ruthenium; D004247:DNA; D053148:Caspase 3; D053179:Caspase 7
keywords: Cell cycle arrest; Cytotoxicity in vitro; DNA-binding; Reactive oxygen species; Ru(II) polypyridyl complex; Western blot analysis