Ruthenium(II)/Benzonitrile Complex Induces Cytotoxic Effect in Sarcoma-180 Cells by Caspase-Mediated and Tp53/p21-Mediated Apoptosis, with Moderate Brine Shrimp Toxicity.
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
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Sarcoma
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Complexos de Coordenação
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Antineoplásicos
Limite:
Animals
Idioma:
En
Revista:
Biol Trace Elem Res
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Brasil