Busca de novo protótipo a base de rutênio candidato à utilização na terapia antineoplásica
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2014-03-30
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Universidade Federal de Goiás
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The estimate of IARC indicates that occur 27 million new cases of cancer in the world by 2030. Due to the increase in the number of cancer cases in the world, there was intensification in the search for new chemotherapeutic agents that are effective for the treatment of cancer. The pharmaceutical industry therefore intensified the search for new metal-based drugs that offer the possibility of oral administration, reduction of serious side effects and reduced clinical costs. Due to the foregoing, we assessed the cytotoxic, genotoxic, interference on the cell cycle kinetics and mechanism of cell death of [RuCl(bcn)(phen)(dppb)]PF6, a new complex of ruthenium (II). Cytotoxicity was assessed by the MTT assay and it has shown that the compound tested showed inhibition of tumor cell viability in Sarcoma 180 (S180) in lower concentrations (IC50 8.89 μM ± 3.9) and cytotoxicity at higher concentrations for normal lymphocytes (IC50 17 μM). [RuCl(bcn)(phen)(dppb)]PF6 also showed a significant lethality to brine shrimp nauplii Artemia salina (CL50 300.31 μg mL). The comet assay indicated that the compound is not genotoxic for lymphocytes cells, because there was no significant increase in DNA damage in cells treated, and exhibits low genotoxicity to tumor cells (S180). The Ru complex 25 induced changes in cell cycle identified by flow cytometric test, increasing the number of cells in G0 / G1 phase and lowering synthesis phase within 24 hours of treatment. The complex induced an increase of cells positive for Annexin-V/PI for flow cytometric test, suggesting cell death by apoptosis. By Western Blot assay, it was possible to infere that the complex may be triggering cell death by caspase-independent intrinsic apoptosis. However, others specifics markers are needed to understand the cascade of events which the intrinsic apoptosis pathway that is effecting this process of cell death, and if only this pathway is being activated in apoptosis, thus elucidating the mechanism of action in cells S180. Thus, this compound showed cytotoxicity to tumor cells, high safety of use, due to absent genotoxicity in normal cells, low genotoxicity in tumor cell, and possibly acts by caspase-independent apoptosis intrinsic pathway.
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FARIA, R. S. Busca de novo protótipo a base de rutênio candidato à utilização na terapia antineoplásica. 2015. 59 f. Dissertação (Mestrado em Biologia) - Universidade Federal de Goiás, Goiânia, 2014.