Ruthenium (II) polypyridyl complexes stabilize the bcl-2 promoter quadruplex and induce apoptosis of Hela tumor cells

Biometals. 2013 Jun;26(3):387-402. doi: 10.1007/s10534-013-9622-6. Epub 2013 Mar 30.

Abstract

In the present study, the interaction between GC-rich sequence of bcl-2 gene P1 promoter (Pu39) and two ruthenium (II) polypyridyl complexes, [Ru(bpy)₂(tip)]²⁺ (1) and [Ru(phen)₂(tip)]²⁺ (2), was investigated by UV-Visible, fluorescence spectroscopy, circular dichroism, fluorescence resonance energy transfer melting assay and polymerase chain reaction stop assay. Those experimental results indicated that the two complexes can effectively stabilize the G-quadruplex of Pu39. It was found that the complex 2 exhibited greater cytotoxic activity than 1 against human Hela cells and can enter into Hela cells in a short period of time to effectively induce apoptosis of cells. Further experiments found that complexes 1 and 2 had as potent inhibitory effects on ECV-304 cell migration as suramin. Those noteworthy results provide new insights into the development of anticancer agents for targeting G-quadruplex DNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • G-Quadruplexes / drug effects*
  • HeLa Cells
  • Humans
  • Models, Molecular
  • Organometallic Compounds / chemical synthesis
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacology*
  • Promoter Regions, Genetic / drug effects*
  • Promoter Regions, Genetic / genetics
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Pyridines / chemistry*
  • Ruthenium / chemistry*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Organometallic Compounds
  • Proto-Oncogene Proteins c-bcl-2
  • Pyridines
  • Ruthenium