title: Induction of cell cycle arrest and apoptosis by ruthenium complex cis-(dichloro)tetramineruthenium(III) chloride in human lung carcinoma cells A549.
abstract: Lung cancer is one of the leading causes of death in the world, and non-small cell lung carcinoma (NSCLC) accounts for approximately 75-85% of all lung cancers. In the present work, we studied the cytotoxic activity, cell cycle arrest and induction apoptosis of the compound cis-(dichloro)tetramineruthenium(III) chloride {cis-[RuCl(2)(NH(3))(4)]Cl} in human lung carcinoma tumor cell line A549. The results of MTT and trypan blue assays showed that cis-[RuCl(2)(NH(3))(4)]Cl causes reduction in the viability of A549 cells when treating with 95 and 383 μM of the compound for 48 and 72 h. Lower concentrations of the compound (19, 3.8 and 0.38 μM), however, only slightly affected cell viability. The IC(50) value for the compound was about 383 μM. Survival analysis of the A549 cells after treatment with ruthenium(III) compound using long term clonogenic assay showed that it reduced colony formation ability at concentrations of 0.38 and 3.8 μM, and at concentrations of 95 and 383 μM no colonies were observed. Cell cycle analysis showed that compound ruthenium led to an accumulation of A549 cells in S phase and increased in the sub-G1 peak. In addition, cis-(dichloro)tetramineruthenium(III) chloride treatment induced apoptosis, as observed by the increased numbers of annexin V-positive cells and increased messenger RNA expression of caspase-3.
authors.affiliation: Instituto de Ciências Biológicas-ICB I- Sala 200- UFG, Campus Samambaia (Campus II), Universidade Federal de Goiás-UFG, Goiânia, Goiás, Brazil. alinypereiralima@gmail.com
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: Jordana Ribeiro
authors.initials: JR
authors.lastname: Soares
authors.forename: Lucas Carlos Gomes
authors.initials: LC
authors.lastname: Pereira
authors.forename: Hellen Karine Paes
authors.initials: HK
authors.lastname: Porto
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
authors.initials: Ede P
authors.lastname: Silveira-Lacerda
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015394:Molecular Structure; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017975:Ruthenium Compounds / Q000737:chemistry / Q000494:pharmacology*; D016196:S Phase / Q000187:drug effects
chemical_list: C543901:(dichloro)tetraammineruthenium(III); D017975:Ruthenium Compounds; D053148:Caspase 3