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Cytotoxicity of half sandwich ruthenium(II) complexes with strong hydrogen bond acceptor ligands and their mechanism of action

Das, Sangeeta and Sinha, Sarika and Britto, Ramona and Somasundaram, Kumaravel and Samuelson, Ashoka G (2010) Cytotoxicity of half sandwich ruthenium(II) complexes with strong hydrogen bond acceptor ligands and their mechanism of action. In: Journal of inorganic biochemistry, 104 (2). pp. 93-104.

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Abstract

Neutral and cationic organometallic ruthenium(II) piano stool complexes of the type [(eta(6)-cymene)R-uCl(X)(Y)] (complexes R1-R8) has been synthesized and characterized. In cationic complexes, X, Y is either a eta(2) phosphorus ligand such as 1,1-bis(diphenylphosphino)methane (DPPM) and 1,2-bis(diphenylphosphino)ethane (DPPE) or partially oxidized ligands such as 1,2-bis(diphenylphosphino)methane monooxide (DPPMO) and 1,2-bis(diphenylphosphino)ethane monooxide (DPPEO) which are strong hydrogen bond acceptors. In neutral complexes. X is chloride and Y is a monodentate phosphorous donor. Complexes with DPPM and DPPMO ligands ([(eta(6)-cymene)Ru(eta(2)-DPPM)Cl]PF6 (R2), [(eta(6)-cymene)Ru(eta(2)-DPPMO)Cl]PF6 (R3), [(eta(6)-cymene)Ru(eta(1)-DPPM)Cl-2] (R5) and [(eta(6)-cymene)Ru(eta(1)-DPPMO)Cl-2] (R6) show good cytotoxicity. Growth inhibition study of several human cancer cell lines by these complexes has been carried out. Mechanistic studies for R5 and R6 show that inhibition of cancer cell growth involves both cell cycle arrest and apoptosis induction. Using an apoptosis PCR array, we identified the sets of antiapoptotic genes that were down regulated and pro-apoptotic genes that were up regulated. These complexes were also found to be potent metastasis inhibitors as they prevented cell invasion through matrigel. The complexes were shown to bind DNA in a non intercalative fashion and cause unwinding of plasmid DNA in cell-free medium by competitive ethidium bromide binding, viscosity measurements, thermal denaturation and gel mobility shift assays.

Item Type: Journal Article
Additional Information: Copyright for this article belongs to Elsevier science.
Keywords: Ruthenium(II) complexes; DNA binding; Cancer; Cytotoxicity; Microarrays; Cell cycle analysis
Department/Centre: Division of Biological Sciences > Microbiology & Cell Biology
Division of Chemical Sciences > Inorganic & Physical Chemistry
Date Deposited: 27 Jan 2010 09:53
Last Modified: 19 Sep 2010 05:54
URI: http://eprints.iisc.ernet.in/id/eprint/25458

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