Mecanismo de morte celular induzida por complexos de rutênio II e III em diferentes linhagens tumorais
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Data
2014-03-19
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Universidade Federal de Goiás
Resumo
The resistance acquired by some tumor cell lines retricts the use of drugs made of
platinum because of Ruthenium compounds have been objects of great attention for
presenting antimetastatic properties and low toxicity. Ruthenium compounds form
compounds with the most different chemical binders, presenting good behavior and
expanding the possibilities offor biological applications. A wide variety of coordination
has enabled studies on ruthenium complexes, andseveral oxidation stages (Ru (II),
Ru (III), and Ru (IV)) under physiological conditions and the rate of binder
substitution. This study ranges the citotoxic activity of ruthenium (III) compound cis-
Tetraammine(oxalato)Ruthenium(III) Dithionate - {Cis-[Ru(C2O4)(NH3)4]2(S2O6)} to
treat human erythroleukemia (K562) tumor cell lineand the complex of ruthenium (II)
coordinated a phosphine ligand and nitrile front tumor lineage S180 through the
techniques of assay cell viability, assay kinetics of cell cycle phases, annexin V
assay/ propidium iodide, test of mitochondrial membrane potential, test comet and
gene expression through real time PCR. Both antiproliferative and cytotoxic activity
revealed that K562 cells cultured with ruthenium (III) compound showed meaningful
decrease in proliferation. Ruthenium(III) compound induced the IC50 value was of
18.28 μM set againts the cell cycle profiles cells not treated. Flow cytometric analysis
indicated a sub-G1 arresting effect of ruthenium compound on K562 cells. Through
the cell viability assay through MTT reduction technique, it was found that the
complex of ruthenium (II) phosphine coordinated and nitrile presented cytotoxic
activity when facing the tumor strain S180 with IC50 17.02±8.21μM and IC50 de 53.73
± 5.71 μM for lymphocyte. When analyzing the cell cycle of tumor cells S180 treated
with complex of ruthenium (II) caused increase in cells in G0/G1 and in S phase
decreased. We observed an increase G2 / M. In the analysis of apoptosis assays, the
results pointed that the complex ruthenium (II) induced cell death via apoptosis in
tumor strain S180 as proved the increase in annexin cells V positive, depolarization
of the mitochondrial membrane potential, activation of caspase 3 (Casp3) and 8
(Casp8) and increased expression levels of caspase-3 (Casp3) (mRNA), Bax
(mRNA) and Tp53. The results lead to the conclusion that both complexes of
ruthenium (II) and (III) induce cytotoxic activity against cell models tested, and that this activity correlates with alterations in cell cycle phases and induction of cell death
via apoptosis.
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PEREIRA, F. C. Mecanismo de morte celular induzida por complexos de rutênio II e III em diferentes linhagens tumorais. 2014. 162 f. Tese (Doutorado em Biologia) - Universidade Federal de Goiás, Goiânia, 2014.