title: The compound cis-(dichloro)tetrammineruthenium(III) chloride induces caspase-mediated apoptosis in K562 cells.
abstract: Ruthenium(III) complexes are increasingly attracting the interest of researchers due to their promising pharmacological properties. In the present study, we investigated the ability of cis-(dichloro)tetrammineruthenium(III) chloride to produce lethal effects in human chronic myelogenous leukemia K562 cells. The MTT tetrazolium reduction test and the trypan blue exclusion assay revealed that the IC(50) for the compound after 48 h of incubation with K562 cells was approximately 10.74 and 73.45 microM, respectively. Interestingly, it was observed that this compound exhibits mild cytotoxicity towards MRC-5 human fibroblast cells (IC(50)>383 microM). Flow cytometric analysis revealed that cis-(dichloro)tetrammineruthenium(III) chloride was capable of change cell cycle distribution since the percentage of cells in the G1, S and G2 phases decreased. In addition, treatment with this compound induced apoptotic cell death in K562 cells, demonstrated by increased DNA content in the sub-G1-peak and a significant increase in caspase-3 activity. Assay using cyclosporin A, an inhibitor of the mitochondrial permeability transition pore (MPT) showed that the preincubation of K562 cells with this inhibitor had not effect on cis-(dichloro)tetrammineruthenium(III) chloride induced caspase-3 activation. In summary, cis-(dichloro)tetrammineruthenium(III) chloride displayed a significant cytotoxic effect through cell cycle arrest and apoptotic induction in K562 cells, which suggests that cis-(dichloro)tetrammineruthenium(III) chloride might have therapeutic potential against leukemia.
authors.affiliation: Laboratório de Genética Molecular e Citogenética, Instituto de Ciências Biológicas, Universidade Federal de Goiás-UFG, Goiânia, Goiás, Brazil.
authors.forename: Aliny Pereira
authors.initials: AP
authors.lastname: de Lima
authors.forename: Flávia de Castro
authors.initials: Fde C
authors.lastname: Pereira
authors.forename: Cesar Augusto Sam Tiago
authors.initials: CA
authors.lastname: Vilanova-Costa
authors.forename: Francyelli Mariana dos Santos
authors.initials: FM
authors.lastname: Mello
authors.forename: Alessandra de Santana Braga Barbosa
authors.initials: Ade S
authors.lastname: Ribeiro
authors.forename: Polyana Lopes
authors.initials: PL
authors.lastname: Benfica
authors.forename: Marize Campos
authors.initials: MC
authors.lastname: Valadares
authors.forename: Luiz Alfredo
authors.initials: LA
authors.lastname: Pavanin
authors.forename: Wagner Batista
authors.initials: WB
authors.lastname: dos Santos
authors.forename: Elisângela de Paula Silveira
authors.initials: Ede P
authors.lastname: Lacerda
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology; D006801:Humans; D020014:K562 Cells; D004915:Leukemia, Erythroblastic, Acute / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017975:Ruthenium Compounds / Q000494:pharmacology*; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism; D014343:Trypan Blue / Q000378:metabolism; D014410:Tumor Stem Cell Assay
chemical_list: C543901:(dichloro)tetraammineruthenium(III); D000970:Antineoplastic Agents; D017975:Ruthenium Compounds; D013778:Tetrazolium Salts; D013844:Thiazoles; D016572:Cyclosporine; D020169:Caspases; C022616:thiazolyl blue; D014343:Trypan Blue