Estudo do potencial genotóxico, citotóxico e antitumoral do composto Cloreto de cis-tetraaminodiclororutênio(III) sobre diferentes células tumorais
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2010-01-29
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Universidade Federal de Goiás
Resumo
Current inorganic drugs such cisplatin and related compounds widely used in the
treatment cancer, however its application is limited by its severe toxicity and drug
resistence. These limitations have prompted a search for news metal-based
antitumor agents. Ruthenium (III) complexes represent a new family of promising
metal-based anticancer drugs. In the present study, was investigated in vitro the
effects of the compound on cell viability, cintetics cell cycle phases, mechanisms of
apoptosis and DNA damage on tumors cells. Results of the viability using MTT
reduction test and the trypan blue exclusion assay on K-562 cells revealed that this
compound significantly reduced the viability of the K-562 tumors cells (IC50
approximately 10.74 and 73.45 μM), respectively, moreover viability assays on
A549 lung tumor cells showed that cis-(dichloro)tetrammineruthenium(III) induced
effect moderate this cell lines (IC50 > 383 μM). Additionally was observed that this
compound exhibits little cytotoxicity towards MRC-5 normal human fibroblast cells
(IC50 > 383 μM) when compared to K562 tumor cell line (IC50 10.74 μM).
Clonogenic Assay was performed on A549 cells, and observed that lower
concentrations (0.38 and 3.8 μM) cis-(dichloro)tetrammineruthenium(III) diminished
colony forming ability and highest concentrations (95 and 383 μM) no colony was
observed. In cell cycle analysis on K-562 and S180 tumor cells cistetrammineruthenium(
III) induced change in the distribution the cell cycle phase
since that % of cells entering G1, S and G2 was decreased, correlating with
increase in the proportion of cells in the sub-G1-peak (indicating apoptosis). In the
analysis of damage to the DNA molecule of S180 cells using the comet assay, it
was observed that the ruthenium compound induced damage to the DNA molecule
to both treatments (24 and 48 h) as evidenced by an increase in damage index. In
addition, cis-[RuCl2(NH3)4]Cl treatment induced apoptosis in cells K-562 as
evidenced for increased DNA content in the sub-G1 peak (75.35%) and a
significant increase in caspase-3, 8 and 9 activity. In tumor cells S180 the
apoptosis was demonstrated for by a increase numbers of Annexin V-positive cells
and fragmentation DNA. Taken together, these findings strongly demonstrate that
cis-[RuCl2(NH3)4]Cl exerts antitumor activity and this activity correlates with DNA
damage, process apoptotic and change cell cycle.
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Citação
LIMA, Aliny Pereira de. To study the potential genotoxic, cytotoxic and antitumor compound
Chloride, cis-tetraaminodiclororutênio (III) on various tumor cells. 2010. 148 f. Dissertação (Mestrado em Ciências Biolóicas) - Universidade Federal de Goiás, Goiânia, 2010.