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Ruthenium(II)/Benzonitrile Complex Induces Cytotoxic Effect in Sarcoma-180 Cells by Caspase-Mediated and Tp53/p21-Mediated Apoptosis, with Moderate Brine Shrimp Toxicity.
Faria, Raquel Santos; Silva, Hugo Delleon; Mello-Andrade, Francyelli; Pires, Wanessa Carvalho; de Castro Pereira, Flávia; de Lima, Aliny Pereira; de Fátima Oliveira Santos, Sônia; Teixeira, Thallita Monteiro; da Silva, Paula Francinete Faustino; Naves, Plínio Lázaro Faleiro; Batista, Alzir Azevedo; da Silva Oliveira, Renato José; Reis, Rui Manuel; de Paula Silveira-Lacerda, Elisângela.
Afiliação
  • Faria RS; Department of Genetics, Laboratory of Molecular Genetics and Cytogenetics, Institute of Biological Sciences, Federal University of Goiás, Avenida Esperança, s/n, Campus Samambaia (Campus II), Cx. Postal 131, Goiania, GO, 74690-900, Brazil.
  • Silva HD; Department of Genetics, Laboratory of Molecular Genetics and Cytogenetics, Institute of Biological Sciences, Federal University of Goiás, Avenida Esperança, s/n, Campus Samambaia (Campus II), Cx. Postal 131, Goiania, GO, 74690-900, Brazil.
  • Mello-Andrade F; Uni-Anhanguera University Center of Goias, Goiania, Goiás, 74423-115, Brazil.
  • Pires WC; Department of Genetics, Laboratory of Molecular Genetics and Cytogenetics, Institute of Biological Sciences, Federal University of Goiás, Avenida Esperança, s/n, Campus Samambaia (Campus II), Cx. Postal 131, Goiania, GO, 74690-900, Brazil.
  • de Castro Pereira F; Department of Chemistry, Federal Institute of Education, Science and Technology of Goiás, Goiania, Goiás, 74055-110, Brazil.
  • de Lima AP; Department of Genetics, Laboratory of Molecular Genetics and Cytogenetics, Institute of Biological Sciences, Federal University of Goiás, Avenida Esperança, s/n, Campus Samambaia (Campus II), Cx. Postal 131, Goiania, GO, 74690-900, Brazil.
  • de Fátima Oliveira Santos S; Department of Genetics, Laboratory of Molecular Genetics and Cytogenetics, Institute of Biological Sciences, Federal University of Goiás, Avenida Esperança, s/n, Campus Samambaia (Campus II), Cx. Postal 131, Goiania, GO, 74690-900, Brazil.
  • Teixeira TM; Department of Genetics, Laboratory of Molecular Genetics and Cytogenetics, Institute of Biological Sciences, Federal University of Goiás, Avenida Esperança, s/n, Campus Samambaia (Campus II), Cx. Postal 131, Goiania, GO, 74690-900, Brazil.
  • da Silva PFF; Faculty of Brazil Institute (FIBRA), Anapolis, Goiás, 75133-050, Brazil.
  • Naves PLF; Department of Genetics, Laboratory of Molecular Genetics and Cytogenetics, Institute of Biological Sciences, Federal University of Goiás, Avenida Esperança, s/n, Campus Samambaia (Campus II), Cx. Postal 131, Goiania, GO, 74690-900, Brazil.
  • Batista AA; Department of Genetics, Laboratory of Molecular Genetics and Cytogenetics, Institute of Biological Sciences, Federal University of Goiás, Avenida Esperança, s/n, Campus Samambaia (Campus II), Cx. Postal 131, Goiania, GO, 74690-900, Brazil.
  • da Silva Oliveira RJ; Department of Genetics, Laboratory of Molecular Genetics and Cytogenetics, Institute of Biological Sciences, Federal University of Goiás, Avenida Esperança, s/n, Campus Samambaia (Campus II), Cx. Postal 131, Goiania, GO, 74690-900, Brazil.
  • Reis RM; Campus of Exact and Technological Sciences, State University of Goiás, Anapolis, Goiás, 75110-390, Brazil.
  • de Paula Silveira-Lacerda E; Department of Chemistry, Federal University of São Carlos, Sao Carlos, São Paulo, 13565-905, Brazil.
Biol Trace Elem Res ; 198(2): 669-680, 2020 Dec.
Article em En | MEDLINE | ID: mdl-32266641
ABSTRACT
Ruthenium(II)/benzonitrile complexes have demonstrated promising anticancer properties. Considering that there are no specific therapies for treating sarcoma, we decided to evaluate the cytotoxic, genotoxic, and lethal effects of cis-[RuCl(BzCN)(phen)(dppb)]PF6 (BzCN = benzonitrile; phen = 1,10-phenanthroline; dppb = 1,4-bis-(diphenylphosphino)butane), as well as the mechanism of cell death induction that occurs against murine sarcoma-180 tumor. Thus, MTT assay was applied to assess the ruthenium cytotoxicity, showing that the compound is a more potent inhibitor for the sarcoma-180 tumor cell viability than normal cells (lymphocytes). The comet assay indicated low genotoxic for normal cells. cis-[RuCl(BzCN)(phen)(dppb)]PF6 also showed moderate lethality in Artemia salina. The complex induced cell cycle arrest in the G0/G1 phase in sarcoma-180 cells. In addition, the complex caused S180 cells to die by apoptosis by an increase in Annexin-V-positive cells and morphological changes typical of apoptotic cells. Additionally, cis-[RuCl(BzCN)(phen)(dppb)]PF6 increased the gene expression of Bax, Casp3, and Tp53 in S180 cells. By using a western blot, we observed an increased protein level of TNF-R2, Bax, and p21. In conclusion, cis-[RuCl(BzCN)(phen)(dppb)]PF6 is active and selective for sarcoma-180 cells, leading to cell cycle arrest at the G0/G1 and cell death through a caspases-mediated and Tp53/p21-mediated pathway.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Rutênio / Sarcoma / Complexos de Coordenação / Antineoplásicos Limite: Animals Idioma: En Revista: Biol Trace Elem Res Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Brasil
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Rutênio / Sarcoma / Complexos de Coordenação / Antineoplásicos Limite: Animals Idioma: En Revista: Biol Trace Elem Res Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Brasil