title: The studies on the cytotoxicity in vitro, cellular uptake, cell cycle arrest and apoptosis-inducing properties of ruthenium methylimidazole complex [Ru(MeIm)4(p-cpip)](2.).
abstract: A new ruthenium methylimidazole complex [Ru(MeIm)4(p-cpip)](2+) (Ru1, p-cpip=2-(4-chlorophenyl)-1H-imidazo[4,5-f][1,10]phenanthroline, MeIm=1-methylimidazole) has been synthesized and characterized. The cellular uptake, in vitro cytotoxicities, cell cycle arrest and apoptosis-inducing mechanism of this Ru(II) complex have been extensively explored by Inductively Coupled Plasma Mass Spectrometry (ICP-MS), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, Comet assay, inverted fluorescence microscope as well as Western blotting experimental techniques. Notably, Ru1 displayed relatively high cytotoxic activity against lung cancer A549 cells and had high selectivity between tumor and normal cells in comparison with cisplatin. Further studies showed that Ru1 caused cell cycle arrest at G0/G1 phase and induced apoptosis via the mitochondrial pathway, which involved reactive oxygen species (ROS) accumulation, mitochondrial dysfunction and Bcl-2 and caspase correlative family member activation. For providing more information about the possible antitumor mechanism, the in vitro DNA binding studies have been also investigated by different spectrophotometric methods, thermal denaturation and viscosity measurements.
authors.affiliation: School of Pharmacy, Guangdong Medical University, Zhanjiang 524023, China.
authors.forename: Lan-mei
authors.initials: LM
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Guangdong Medical University, Zhanjiang 524023, China.
authors.forename: Fa
authors.initials: F
authors.lastname: Peng
authors.affiliation: School of Pharmacy, Guangdong Medical University, Zhanjiang 524023, China.
authors.forename: Guo-dong
authors.initials: GD
authors.lastname: Li
authors.affiliation: Analysis Centre of Guangdong Medical University, Zhanjiang 524023, China; Guangdong Key Laboratory for Research and Development of Nature Drugs, Guangdong Medical University, Zhanjiang 524023, China.
authors.forename: Xin-ming
authors.initials: XM
authors.lastname: Jie
authors.affiliation: Analysis Centre of Guangdong Medical University, Zhanjiang 524023, China; Guangdong Key Laboratory for Research and Development of Nature Drugs, Guangdong Medical University, Zhanjiang 524023, China.
authors.forename: Kang-rong
authors.initials: KR
authors.lastname: Cai
authors.affiliation: Analysis Centre of Guangdong Medical University, Zhanjiang 524023, China; Guangdong Key Laboratory for Research and Development of Nature Drugs, Guangdong Medical University, Zhanjiang 524023, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Cai
authors.affiliation: Analysis Centre of Guangdong Medical University, Zhanjiang 524023, China; Guangdong Key Laboratory for Research and Development of Nature Drugs, Guangdong Medical University, Zhanjiang 524023, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: The First Clinical Medical College, Guangdong Medical University, Zhanjiang 524023, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zeng
authors.affiliation: The First Clinical Medical College, Guangdong Medical University, Zhanjiang 524023, China.
authors.forename: Wu
authors.initials: W
authors.lastname: Li
authors.affiliation: The First Clinical Medical College, Guangdong Medical University, Zhanjiang 524023, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Analysis Centre of Guangdong Medical University, Zhanjiang 524023, China; Guangdong Key Laboratory for Research and Development of Nature Drugs, Guangdong Medical University, Zhanjiang 524023, China. Electronic address: jincanchen@126.com.
authors.forename: Jin-can
authors.initials: JC
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D006801:Humans; D066298:In Vitro Techniques; D013058:Mass Spectrometry; D017975:Ruthenium Compounds / Q000494:pharmacology*
chemical_list: D017975:Ruthenium Compounds
keywords: Apoptosis; Cell cycle arrest; Cytotoxicity; Mitochondrial dysfunction; Ruthenium methylimidazole complex