Cytotoxic activity, DNA damage, cellular uptake, apoptosis and western blot analysis of ruthenium(II) polypyridyl complex against human lung decarcinoma A549 cell

• Published in: Journal of inorganic biochemistry 2015-11, Vol.152, p.1-9
• Main Authors: Lai, Shang-Hai, Jiang, Guang-Bin, Yao, Jun-Hua, Li, Wei, Han, Bing-Jie, Zhang, Cheng, Zeng, Chuan-Chuan, Liu, Yun-Jun
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; Antineoplastic Agents - toxicity; Apoptosis; Biological Transport; Cell cycle arrest; Cell Nucleus - drug effects; Cell Nucleus - metabolism; Coordination Complexes - chemical synthesis; Coordination Complexes - pharmacology; Cytoplasm - drug effects; Cytoplasm - metabolism; DNA Damage; HeLa Cells; Humans; Membrane Potential, Mitochondrial; Mitochondrial membrane potential; Phenanthrolines - chemical synthesis; Phenanthrolines - pharmacology; Reactive Oxygen Species - metabolism; Ruthenium - chemistry; Ruthenium(II) complex; Western blot analysis
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2015.08.012

A new ruthenium(II) polypyridyl complex [Ru(dmp)2(pddppn)](ClO4)2Ru1 was synthesized and characterized. The cytotoxic activity in vitro of the complex was evaluated by MTT method. Ru1 shows high effect on the inhibition of the cell growth against BEL-7402, HeLa, MG-63 and A549 cells with low IC50 values of 1.6±0.4, 9.0±0.8, 1.5±0.2 and 1.5±0.3μM, respectively. The cellular uptake indicates that Ru1 can enter into the cytoplasm and accumulate in the cell nuclei. Ru1 can induce apoptosis in A549 cells and enhance the levels of reactive oxygen species (ROS) and induce the decrease of mitochondrial membrane potential. In addition, Ru1 can down-regulate the levels of Bcl-2, Bcl-x, Bak, and Bim expression and up-regulate the expression of Bag-1 and Bad. The complex induces apoptosis of A549 cells through an intrinsic ROS-mediated mitochondrial dysfunction pathway, which was accompanied by regulating the expression of caspases and Bcl-2 family proteins. A new Ru(II) complex [Ru(dmp)2(pddppn)](ClO4)2Ru1 was synthesized and characterized. The cytotoxicity, apoptosis, cellular uptake, comet assay, cell cycle arrest, ROS, mitochondrial membrane potential, western blot analysis were investigated. [Display omitted] •A new Ru(II) complex [Ru(dmp)2(pddppn)](ClO4)2 was synthesized and characterized.•The cytotoxicity of complex against four cancer cells was evaluated.•The apoptosis, cellular uptake, ROS and mitochondrial membrane potential were studied.•The cell cycle arrest and western blot analysis were investigated.