Ruthenium(II)/Benzonitrile Complex Induces Cytotoxic Effect in Sarcoma-180 Cells by Caspase-Mediated and Tp53/p21-Mediated Apoptosis, with Moderate Brine Shrimp Toxicity.

Autor: 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.; Uni-Anhanguera University Center of Goias, Goiania, Goiás, 74423-115, Brazil., Mello-Andrade F; 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.; Department of Chemistry, Federal Institute of Education, Science and Technology of Goiás, Goiania, Goiás, 74055-110, 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 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 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.; Faculty of Brazil Institute (FIBRA), Anapolis, Goiás, 75133-050, 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; 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., Naves PLF; Campus of Exact and Technological Sciences, State University of Goiás, Anapolis, Goiás, 75110-390, Brazil., Batista AA; Department of Chemistry, Federal University of São Carlos, Sao Carlos, São Paulo, 13565-905, Brazil., da Silva Oliveira RJ; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, 14784-400, Brazil., Reis RM; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, 14784-400, Brazil., de Paula Silveira-Lacerda E; 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. silveiralacerda@gmail.com.
Jazyk: angličtina
Zdroj: Biological trace element research [Biol Trace Elem Res] 2020 Dec; Vol. 198 (2), pp. 669-680. Date of Electronic Publication: 2020 Apr 08.
DOI: 10.1007/s12011-020-02098-8
Abstrakt: 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)]PF 6 (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)]PF 6 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)]PF 6 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)]PF 6 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.
Databáze: MEDLINE
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