Avaliação do potencial antitumoral de dois novos complexos de rutênio (II) contendo alanina e triptofano em suas estruturas
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Data
2012-02-24
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Universidade Federal de Goiás
Resumo
It is well known that metal complexes have been used as therapeutic agents since
ancient times. However, with the success of cisplatin development as an antitumor agent
in 1960inorganic drugs come to mainstream again. Despite the success of platinum
compounds, serious problems are encountered when administering these drugs, such as
nephrotoxicity, neurotoxicity and acquired resistance. In face of these problems other
chemotherapeutic agents, less toxic to the organism and more efficient, become
necessary. Several studies have been shown that ruthenium compounds present high
selectivity for tumor cells and low systemic toxicity when compared to platinum (II)
compounds. The present study evaluate antimor activity of two new ruthenium(II)
compounds associated with amino acids, alanine and tryptophan. Ruthenium(II)
compound were tested against B16-F10 and Ehrlich tumor cell lines and L-929 basal
line using MTT assay, at different concentrations (0.2 - 200 mM) for 48 hours of
treatment. Cell cycle analysis and apoptosis induction analyses by flow citometry and
comet assay for DNA damage were also performed The IC50 values were estimated as
16.17 mM (RuAla) and 7.75 mM (RuTrp). The compound RuAla proved to be specific
for the B16-F10 tumor cell line and showed a significant ability to change cell cycling
profiles, arresting cells inG0/G1 phase, and also inducing cell death by apoptosis within
48 hours of treatment. The compound RuTrp showed high cytotoxic potential against
Ehrlich tumor, interfering cell cycle kinetics,causing cell cycle arrest in G0/G1 phase
and inducing cell death by apoptosis. Comet assay presented damage to genetic
material only when cells were trated with high concentrations of RuTrp. , RuAla and
RuTrp presented relevant cytotoxic activities towards tumor lineages tested in vitro.
Thus, more specific tests are needed to elucidate the mechanism of action of these
promising The ruthenium(II) compounds.
Descrição
Palavras-chave
Rutênio , Câncer , B16-F10 , Tumor de Ehrlich , Citotoxicidade , Apoptose , Ruthenium , Cancer , Ehrlich tumor , Cytotoxicity , Apoptosis
Citação
PORTO, H. K. P. Avaliação do potencial antitumoral de dois novos complexos de rutênio (II) contendo alanina e triptofano em suas estruturas. 2012. 95 f. Dissertação (Mestrado em Ciências Farmacêuticas) - Universidade Federal de Goiás, Goiânia, 2012.