Estudo da atividade citotóxica do poliacetileno 5-octa-2, 4, 6-triinil-furan-2(5H)-ona / Study of the cytotoxic activity of polyacetylene 5-octa-2,4,6-triinil-furan-2 (5H)-one

AUTOR(ES)
FONTE

IBICT - Instituto Brasileiro de Informação em Ciência e Tecnologia

DATA DE PUBLICAÇÃO

26/06/2012

RESUMO

Skin cancers are the most common types of cancer in Brazil, and correspond to around 25% of all malignant tumors recorded. Of these, melanoma represents at least 5% and is characterized by its high metastatic power. The development of anticancer agents from natural products is considered critical to pharmacology, and interest in the development of more effective chemotherapeutic agents is increasing each year. This study evaluates the antineoplastic activity of the substance isolated from Vernoniascorpioides (Lam) Perspolyacetylene 5-octa-2,4,6-triinil-furan-2 (5H)-one. To assess the cytotoxic activity of the substance, vital MTT dyes were used in vital cells of murine melanoma B16F10, and the dye XTT for the leukemia cells, solid tumors and NHMC (normal human mononuclear cells). The patterns of cell death were determined by fluorescence microscopy using the dyesethidium bromide, fluorescein diacetate and acridine orange. The enzyme activity of caspase 3 was determined by colorimetric assay. The antitumor effect of polyacetylene 5-octa-2 ,4,6-triinil-furan-2 (5H)-one in in vivo models of solid tumors and lung metastasis in C57BL6 mice, was evaluated using the following parameters: tumor growth, rate of metastasis, body weight, and exploratory activity through the Open Field model. The toxicity of the compound was evaluated in different organs. The antinociceptive activity of the isolated substance was evaluated in animals submitted to the lung metastasis model. The results showed that the substance polyacetylene has significant levels of cytotoxicity on B16F10 cells, with IC50 of 17.39 3.26 μM, while the NB4 leukemic cells, RAMOS, JURKAT and NALM6 solid tumors and PC3, H1299, and NCI MG63 and did not show significant cytotoxicity against CMNH. The polyacetylene 5-octa-2,4,6-triinil-furan-2 (5H)-one showed apoptosis as the main mechanism of cell death,viathe induction of caspase 3. Inhibition of 80 15.95% was also observed in the development of solid tumors in mice, induced by B16F10, and an increase in the number of crossings in the Open Field model of 57.50 5.90 at the lowest dose, compared with the control group tumor (34.5 5.23). A 62% reduction in metastatic nodules was seen at the lowest dose, as well as a reduction in the number of crossings. No significant toxicological effect or changes in body weight of the healthy animals were observed. In the evaluation of sensitivity to mechanical substances, there was a significant reduction in sensitivity of the treated groups. Taken together, these results demonstrate that the polyacetylene 5-octa-2,4,6-triinil-furan-2 (5H)-one showed significant anticancer activity, and may become an important tool for the treatment of cancer, without the existence of undesirable side effects. Based on the promising results obtained with polyacetylene, further pharmacological and molecular studies are needed, to elucidate the mechanism of action of this substance with potential as a new and attractive molecule for cancer treatment

ASSUNTO(S)

vernonia scorpioides poliacetileno citotoxicidade apoptose farmacia produtos naturais vernoniascorpioides (lam) pers polyacetylene cytotoxicity apoptosis

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