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- Title
Ruthenium(II)/Benzonitrile Complex Induces Cytotoxic Effect in Sarcoma-180 Cells by Caspase-Mediated and Tp53/p21-Mediated Apoptosis, with Moderate Brine Shrimp Toxicity.
- Authors
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
- 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.
- Subjects
ARTEMIA; CELL cycle; RUTHENIUM; CELL death; CELLS; APOPTOSIS; GENETIC toxicology
- Publication
Biological Trace Element Research, 2020, Vol 198, Issue 2, p669
- ISSN
0163-4984
- Publication type
Article
- DOI
10.1007/s12011-020-02098-8