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Eur J Pharmacol ; 764: 340-345, 2015 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-26169565

RESUMO

Over the last few decades, research on snake venom toxins has provided not only new tools to decipher molecular details of various physiological processes, but also inspiration to design and develop a number of therapeutic agents. Isolated from the venom of Macrovipera lebetina obutusa (MLO), obtustatin represents the shortest known snake venom monomeric disintegrin specific inhibitor of α1ß1 integrin. This low molecular weight peptide revealed a potent therapeutic effect on melanoma progression. Its oncostatic effect was related to the inhibition of angiogenesis. The aim of the proposed investigation was to study the influence of obtustatin and crude MLO venom on the S-180 sarcoma growth in vitro and in vivo. A S-180 sarcoma bearing mouse model, histological examination, DNA retardation assay were utilized to investigate the anti-tumor effects of MLO and obtustatin. In addition, some biochemical tests (chemiluminescence-ChL, TBA-test) were applied to elucidate the influence of obtustatin and crude MLO venom on the S-180 sarcoma. The size of tumor was significantly inhibited by MLO venom and obtustatin with the inhibitory rate of 50% and 33% at the doses of 10 µg/mouse and 1mg/kg/day respectively. Both ChL and MDA decrease in the two treated groups. Both obtustatin and MLO venom have an anticancer activity and might be candidates for the treatment of malignant sarcoma. All our results have shown that both obtustatin and MLO venom have an anticancer activity and might be candidates for the treatment of malignant sarcoma.


Assuntos
Antineoplásicos/farmacologia , Sarcoma Experimental/tratamento farmacológico , Venenos de Víboras/farmacologia , Animais , Antineoplásicos/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , DNA/metabolismo , Dano ao DNA , Relação Dose-Resposta a Droga , Peroxidação de Lipídeos/efeitos dos fármacos , Medições Luminescentes , Malondialdeído/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Sarcoma Experimental/genética , Sarcoma Experimental/patologia , Fatores de Tempo , Carga Tumoral/efeitos dos fármacos , Venenos de Víboras/metabolismo
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