title: Cytoxicity and apoptotic mechanism of ruthenium(II) amino acid complexes in sarcoma-180 tumor cells.
abstract: Over the past several decades, much attention has been focused on ruthenium complexes in antitumor therapy. Ruthenium is a transition metal that possesses several advantages for rational antitumor drug design and biological applications. In the present study, five ruthenium complexes containing amino acids were studied in vitro to determine their biological activity against sarcoma-180 tumor cells. The cytotoxicity of the complexes was evaluated by an MTT assay, and their mechanism of action was investigated. The results demonstrated that the five complexes inhibited the growth of the S180 tumor cell line, with IC50 values ranging from 22.53 µM to 50.18 µM, and showed low cytotoxicity against normal L929 fibroblast cells. Flow cytometric analysis revealed that the [Ru(gly)(bipy)(dppb)]PF6 complex (2) inhibited the growth of the tumor cells by inducing apoptosis, as evidenced by an increased number of Annexin V-positive cells and G0/G1 phase cell cycle arrest. Further investigation showed that complex 2 caused a loss of mitochondrial membrane potential; activated caspases 3, caspase-8, and caspase-9 and caused a change in the mRNA expression levels of caspase 3, caspase-9 as well as the bax genes. The levels of the pro-apoptotic Bcl-2 family protein Bak were increased. Thus, we demonstrated that ruthenium amino acid complexes are promising drugs against S180 tumor cells, and we recommend further investigations of their role as chemotherapeutic agents for sarcomas.
authors.affiliation: Laboratory of Molecular Genetics and Cytogenetics, Institute of Biological Sciences, University Federal of Goiás-UFG, Goiânia, Goiás, Brazil.
authors.forename: Aliny Pereira
authors.initials: AP
authors.lastname: Lima
authors.affiliation: Laboratory of Molecular Genetics and Cytogenetics, Institute of Biological Sciences, University Federal of Goiás-UFG, Goiânia, Goiás, Brazil.
authors.forename: Flávia Castro
authors.initials: FC
authors.lastname: Pereira
authors.affiliation: Coordination of Science and Technology, University Federal of Maranhão, São Luís, Maranhão, Brazil.
authors.forename: Marcio Aurelio Pinheiro
authors.initials: MA
authors.lastname: Almeida
authors.affiliation: Laboratory of Molecular Genetics and Cytogenetics, Institute of Biological Sciences, University Federal of Goiás-UFG, Goiânia, Goiás, Brazil.
authors.forename: Francyelli Mariana Santos
authors.initials: FM
authors.lastname: Mello
authors.affiliation: Laboratory of Molecular Genetics and Cytogenetics, Institute of Biological Sciences, University Federal of Goiás-UFG, Goiânia, Goiás, Brazil.
authors.forename: Wanessa Carvalho
authors.initials: WC
authors.lastname: Pires
authors.affiliation: Laboratory of Molecular Genetics and Cytogenetics, Institute of Biological Sciences, University Federal of Goiás-UFG, Goiânia, Goiás, Brazil.
authors.forename: Thallita Monteiro
authors.initials: TM
authors.lastname: Pinto
authors.affiliation: Department of Morphology, Institute of Biosciences - University Estadual Paulista (UNESP), Botucatu, São Paulo, Brazil.
authors.forename: Flávia Karina
authors.initials: FK
authors.lastname: Delella
authors.affiliation: Department of Morphology, Institute of Biosciences - University Estadual Paulista (UNESP), Botucatu, São Paulo, Brazil.
authors.forename: Sérgio Luis
authors.initials: SL
authors.lastname: Felisbino
authors.affiliation: Department of Inorganic Chemistry, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Virtudes
authors.initials: V
authors.lastname: Moreno
authors.affiliation: Department of Chemistry, University Federal of São Carlos, São Carlos, São Paulo, Brazil.
authors.forename: Alzir Azevedo
authors.initials: AA
authors.lastname: Batista
authors.affiliation: Laboratory of Molecular Genetics and Cytogenetics, Institute of Biological Sciences, University Federal of Goiás-UFG, Goiânia, Goiás, Brazil.
authors.forename: Elisângela
authors.initials: E
authors.lastname: de Paula Silveira-Lacerda
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000633:toxicity*; D017209:Apoptosis; D045744:Cell Line, Tumor; D051379:Mice; D012428:Ruthenium / Q000737:chemistry; D017975:Ruthenium Compounds / Q000138:chemical synthesis / Q000633:toxicity*; D012509:Sarcoma / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D000970:Antineoplastic Agents; D017975:Ruthenium Compounds; D012428:Ruthenium