The motivation to use
ruthenium complexes in
cancer treatment has led our research group to synthesize complexes with this
metal and test them against several types of
tumor cells, yielding promising results. In this paper the results of
biological tests, assessed by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, were carried out on the complexes cis-[RuCl(BzCN)(bipy)(
dppe)]PF6 (1), cis-[RuCl(BzCN)(bipy)(dppb)]PF6 (2), cis-[RuCl(BzCN)(bipy)(dppf)]PF6 (3) and cis-[RuCl(BzCN)(phen)(dppb)]PF6 (4) which are described [BzCN = b enzonitrile; bipy =
2,2'-bipyridine; phen = 1,10-
phenanthroline;
dppe = 1,2-bis(diphenylphosphino)
ethane; dppb = 1,4-bis-(diphenylphosphino)
butane; dppf = 1,1'-bis(diphenylphosphino)
ferrocene]. The present study is focused on the cytotoxic activity of complexes (1)-(4) against four tumor cell lines and on the apoptosis and changes in the cell cycle and gene expression observed in the
sarcoma 180 (S180) tumor cell line treated with complex (1). The results demonstrated that this complex inhibits S180 cell growth, with an IC50 of 17.02 ± 8.21 μM, while exhibiting lower cytotoxicity (IC50 = 53.73 ± 5.71 μM) towards lymphocytes (normal cells). Flow cytometry revealed that the complex inhibits the growth of
tumor cells by inducing apoptosis as evidenced by an increase in the proportion of cells positive for
annexin V staining and G0/G1 phase cell-cycle arrest. Further investigation showed that complex (1) induces a drop in the mitochondrial membrane potential and provokes a decrease in Bcl-2
protein expression and increase in
caspase 3 activation, while the increased activation of
caspase 8 caused a decrease in the gene expression in
caspases 3 and 9. Increases in Tp53 and Bax expressions were also observed.