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The Ruthenium Complex cis-(Dichloro)tetraammineruthenium(III) Chloride Presents Selective Cytotoxicity Against Murine B Cell Lymphoma (A-20), Murine Ascitic Sarcoma 180 (S-180), Human Breast Adenocarcinoma (SK-BR-3), and Human T Cell Leukemia (Jurkat) Tumor Cell Lines
Authors:Elisângela de Paula Silveira-Lacerda  Cesar Augusto Sam Tiago Vilanova-Costa  Amélia Hamaguchi  Luiz Alfredo Pavanin  Luiz Ricardo Goulart  Maria Inês Homsi-Brandenburgo  Wagner Batista dos Santos  Andreimar Martins Soares  Auro Nomizo
Institution:1. Laboratório de Genética Molecular e Citogenética, Instituto de Ciências Biológicas—ICB I—Sala 200, Universidade Federal de Goiás—UFG, Campus Samambaia (Campus II), Goiania, Goiás, Brazil
2. Instituto de Genética e Bioquímica, Universidade Federal de Uberlandia—UFU, Uberlandia, Minas Gerais, Brazil
3. Instituto de Química, Universidade Federal de Uberlandia—UFU, Uberlandia, Minas Gerais, Brazil
5. Faculdade Patos de Minas—FPM, Patos de Minas, Minas Gerais, Brazil
4. Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeir?o Preto, Universidade de S?o Paulo—USP, Ribeir?o Preto, S?o Paulo, Brazil
Abstract:The aim of present study was to verify the in vitro antitumor activity of a ruthenium complex, cis-(dichloro)tetraammineruthenium(III) chloride (cis-RuCl2(NH3)4]Cl) toward different tumor cell lines. The antitumor studies showed that ruthenium(III) complex presents a relevant cytotoxic activity against murine B cell lymphoma (A-20), murine ascitic sarcoma 180 (S-180), human breast adenocarcinoma (SK-BR-3), and human T cell leukemia (Jurkat) cell lines and a very low cytotoxicity toward human peripheral blood mononuclear cells. The ruthenium(III) complex decreased the fraction of tumor cells in G0/G1 and/or G2-M phases, indicating that this compound may act on resting/early entering G0/G1 cells and/or precycling G2-M cells. The cytotoxic activity of a high concentration (2 mg mL?1) of cis-RuCl2(NH3)4]Cl toward Jurkat cells correlated with an increased number of annexin V-positive cells and also the presence of DNA fragmentation, suggesting that this compound induces apoptosis in tumor cells. The development of new antineoplastic medications demands adequate knowledge in order to avoid inefficient or toxic treatments. Thus, a mechanistic understanding of how metal complexes achieve their activities is crucial to their clinical success and to the rational design of new compounds with improved potency.
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