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.)

J Inorg Biochem. 2016 Mar:156:64-74. doi: 10.1016/j.jinorgbio.2015.12.016. Epub 2015 Dec 31.

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.

Keywords: Apoptosis; Cell cycle arrest; Cytotoxicity; Mitochondrial dysfunction; Ruthenium methylimidazole complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Cell Cycle Checkpoints / drug effects*
  • Cell Line, Tumor
  • Humans
  • In Vitro Techniques
  • Mass Spectrometry
  • Ruthenium Compounds / pharmacology*

Substances

  • Ruthenium Compounds