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Toxicol In Vitro ; 44: 382-391, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28774850

RESUMO

Lung cancer is the most frequent type of cancer worldwide. In Brazil, only 14% of the patients diagnosed with lung cancer survived 5years in the last decades. Although improvements in the therapeutic approach, it is relevant to identify new chemotherapeutic agents. In this framework, ruthenium metal compounds emerge as a promising alternative to platinum-based compounds once they displayed lower cytotoxicity and more selectivity for tumor cells. The present study aimed to evaluate the antitumor potential of innovative ruthenium(II) complex, [Ru(pipe)(dppb)(bipy)]PF6 (PIPE) on A549 cells, which is derived from non-small cell lung cancer. Results demonstrated that PIPE effectively reduced the viability and proliferation rate of A549 cells. When PIPE was used at 9µM there was increase in G0/G1 cell population with concomitant reduction in frequency of cells in S-phase, indicating cell cycle arrest in G1/S transition. Antiproliferative activity of PIPE was associated to its ability of reducing cyclin D1 expression and ERK phosphorylation levels. Cytotoxic activity of PIPE on A549 cells was observed when PIPE was used at 18µM, which was associated to its ability of inducing apoptosis by intrinsic pathway. Taken together, the data demonstrated that PIPE is a promising antitumor agent and further in vivo studies should be performed.


Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Rutênio/farmacologia , Células A549 , Apoptose/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ciclina D1/metabolismo , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Proteína Quinase 3 Ativada por Mitógeno/metabolismo
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