The Ruthenium Complex cis-(Dichloro)tetraammineruthenium(III) Chloride Presents Selective Cytotoxicity Against Murine B Cell Lymphoma (A-20), Murine Ascitic Sarcoma 180 (S-180), Human Breast Adenocarcinoma (SK-BR-3), and Human T Cell Leukemia (Jurkat) Tumor Cell Lines

Abstract

The aim of present study was to verify the in vitro antitumor activity of a ruthenium complex, cis-(dichloro)tetraammineruthenium(III) chloride (cis-[RuCl(2)(NH(3))(4)]Cl) toward different tumor cell lines. The antitumor studies showed that ruthenium(III) complex presents a relevant cytotoxic activity against murine B cell lymphoma (A-20), murine ascitic sarcoma 180 (S-180), human breast adenocarcinoma (SK-BR-3), and human T cell leukemia (Jurkat) cell lines and a very low cytotoxicity toward human peripheral blood mononuclear cells. The ruthenium(III) complex decreased the fraction of tumor cells in G0/G1 and/or G2-M phases, indicating that this compound may act on resting/early entering G0/G1 cells and/or precycling G2-M cells. The cytotoxic activity of a high concentration (2 mg mL(-1)) of cis-[RuCl(2)(NH(3))(4)]Cl toward Jurkat cells correlated with an increased number of annexin V-positive cells and also the presence of DNA fragmentation, suggesting that this compound induces apoptosis in tumor cells. The development of new antineoplastic medications demands adequate knowledge in order to avoid inefficient or toxic treatments. Thus, a mechanistic understanding of how metal complexes achieve their activities is crucial to their clinical success and to the rational design of new compounds with improved potency.

Cytotoxic effects of the compound cis-tetraammine(oxalato)ruthenium(III) dithionate on K-562 human chronic myelogenous leukemia cells

“…But even if the success of clinical trials in identifying new agents and treatment modalities has been significant, current treatments have many limitations related to their side effects and the development of acquired drug resistance (Robert and Jarry 2003) The new therapeutic agents thus needed should be more active and produce less side effects and they also should act through a mechanism different from that of cytotoxic agents already used (Menezes et al 2007; Silveira-Lacerda et al 2009). …”

The ruthenium complex cis-(dichloro)tetrammineruthenium(III) chloride induces apoptosis and damages DNA in murine sarcoma 180 cells

“…The Ruthenium complex induces apoptosis in S-180 cells 375 fragmentation in Jurkat leukaemia cells (Silveira-Lacerda et al 2009). Unlike the results of DNA damage presented in this study in S-180 cells, genotoxic studies using the alkaline version of the comet assay to evaluate the possible DNA-damaging effects of cis-[RuCl 2 (NH 3 ) 4 ]Cl in human peripheral blood lymphocytes (PBL) showed that this compound does not cause signifi cantly increased DNA damage in normal cells (Ribeiro et al 2009), suggesting that the genotoxic activity of this compound could be selective to tumour cells.…”

“…Unlike the results of DNA damage presented in this study in S-180 cells, genotoxic studies using the alkaline version of the comet assay to evaluate the possible DNA-damaging effects of cis-[RuCl 2 (NH 3 ) 4 ]Cl in human peripheral blood lymphocytes (PBL) showed that this compound does not cause signifi cantly increased DNA damage in normal cells (Ribeiro et al 2009), suggesting that the genotoxic activity of this compound could be selective to tumour cells. Thus, it is possible that the cytotoxicity of cis-[RuCl 2 (NH 3 ) 4 ]Cl to several cancer cell lines in vitro (Silveira-Lacerda et al 2009) is partially due to its DNA damaging effects, as DNA damage is a potent stimulus for apoptotic cell death. This fi nding led us to evaluate the nature of cell death involved in the cytotoxicity of cis-[RuCl 2 (NH 3 ) 4 ]Cl in S-180 cells.…”

“…Among the ruthenium complexes studied for anticancer application, the cis-(dichloro)tetrammineruthenium(III) chloride (cis-[RuCl 2 (NH 3 ) 4 ]Cl) complex has shown promising results on tumour cells in humans and mice (Silveira-Lacerda et al 2009). Recently, it was demonstrated that cis-[RuCl 2 (NH 3 ) 4 ]Cl exerts antitumour activity against both in vitro and in vivo models of the sarcoma 180 (S-180) cell line (Menezes et al 2007;Silveira-Lacerda et al 2009).…”

“…Recently, it was demonstrated that cis-[RuCl 2 (NH 3 ) 4 ]Cl exerts antitumour activity against both in vitro and in vivo models of the sarcoma 180 (S-180) cell line (Menezes et al 2007;Silveira-Lacerda et al 2009). However, no studies on induction of apoptosis and DNA damage have been reported for this cell line.…”