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.
Srivastava
Radhey S
RS
Department of Chemistry, University of Louisiana at Lafayette, LA 70504, USA. rss1805@louisiana.edu
Fronczek
Frank R
FR
Perkins
Richard S
RS
Fukuyama
Tomofusa
T
Xu
Wu
W
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000187:drug effects*; D053938:DNA Fragmentation / Q000187:drug effects; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017975:Ruthenium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D011725:Pyridines; D017975:Ruthenium Compounds; D004247:DNA