Anticancer activities of the ruthenium carboxylato, amido and pyridine complexes

Ruthenium complexes [1-3] with oxalato, amido and pyridine ligands have been synthesized and characterized. Biological tests showed that the ruthenium complexes 2 and 3 have modest cytotoxicity on both murine cell line NIH3T3 and human cancer colon cell lines HCT116 and HT29 while complex 1 has no obvious growth defect. We further tested why complexes 2 and 3 exhibit modest cytotoxicity. Gel electrophoresis analysis demonstrates that complex 3 has the ability to cleave double-stranded DNAs in a dose-dependent manner. In contrast, complex 2 does not have detectable DNA cleavage activity. Additionally, real-time PCR analysis suggests that the observed cell growth inhibition or death could be due to the altered gene expression in the processes of cell cycle and apoptosis/necrosis caused by the addition of complexes 2 and 3. Furthermore, cell death by DNA fragmentation assay indicates that the addition of these two complexes may cause cell necrosis rather than apoptosis.