A ruthenium(II) complex capable of inducing and stabilizing bcl-2 G-quadruplex formation as a potential cancer inhibitor

J Inorg Biochem. 2014 May:134:1-11. doi: 10.1016/j.jinorgbio.2013.12.005. Epub 2013 Dec 24.

Abstract

Two ruthenium(II) complexes (Ru-complexes) were synthesized and characterized in this study. The selectivity and ability of the complexes to interact with bcl-2 DNA were investigated here. It turned out that [Ru(ip)3](ClO4)2·2H2O (complex 1, ip = 1H-iminazole [4,5-f][1,10] phenanthroline) could induce and stabilize the formations of G-quadruplexes more effectively than [Ru(pip)3](ClO4)2·2H2O (complex 2, pip = 2-phenylimidazo-[4,5-f][1,10]phenanthroline) did. Considering the important role of the Ru-complex ligand in inducing and stabilizing the formations of G-quadruplex in our previous studies, we speculate that the overlarge ligand of complex 2 may block its binding affinity for G-quadruplexes. Complex 1 also induced cell apoptosis in in vitro assays. In general, this study provided potentially important information for further development of the Ru-complexes as good inducers and stabilizers of bcl-2 G-quadruplex DNA for cancer treatment.

Keywords: Anticancer; Bcl-2; DNA structures; G-quadruplexes; Ruthenium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology*
  • Cell Survival / drug effects
  • Coordination Complexes / chemical synthesis
  • Coordination Complexes / pharmacology*
  • DNA, Neoplasm / antagonists & inhibitors*
  • DNA, Neoplasm / chemistry
  • Fluorescence Resonance Energy Transfer
  • Fluorescent Dyes
  • G-Quadruplexes / drug effects
  • Gene Expression
  • HeLa Cells
  • Humans
  • Ligands
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Phenanthrolines / chemistry*
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Ruthenium / chemistry*

Substances

  • Antineoplastic Agents
  • Coordination Complexes
  • DNA, Neoplasm
  • Fluorescent Dyes
  • Ligands
  • Phenanthrolines
  • Proto-Oncogene Proteins c-bcl-2
  • Ruthenium