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: | Flávia de Castro Pereira, Plínio Lázaro Faleiro Naves, Raquel Santos Faria, Rui Manuel Reis, Paula F. F. Silva, Elisângela de Paula Silveira-Lacerda, Alzir A. Batista, Aliny Pereira de Lima, Sônia F. O. Santos, Francyelli Mello-Andrade, Renato Oliveira, Hugo Delleon Silva, Thallita Monteiro Teixeira, Wanessa Carvalho Pires |
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| Rok vydání: | 2019 |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
Programmed cell death Cell cycle checkpoint Endocrinology Diabetes and Metabolism Clinical Biochemistry Antineoplastic Agents Apoptosis 010501 environmental sciences 01 natural sciences Biochemistry Ruthenium Inorganic Chemistry 03 medical and health sciences Mice Coordination Complexes Cell Line Tumor Nitriles Cytotoxic T cell Animals MTT assay Cytotoxicity Caspase 0105 earth and related environmental sciences 0303 health sciences biology Chemistry 030302 biochemistry & molecular biology Biochemistry (medical) Sarcoma General Medicine Molecular biology Comet assay Caspases biology.protein Artemia Tumor Suppressor Protein p53 |
| Zdroj: | Biological trace element research. 198(2) |
| ISSN: | 1559-0720 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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