Ação biológica in vitro de tiossemicarbazonas derivadas de canfeno e limoneno em células de melanoma humano (SK-MEL-37)

• Autor(a) principal: Passos, Débora Cristina Silva dos
• Data de Publicação: 2013
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Repositório Institucional da UFG
• dARK ID: ark:/38995/001300000661g
• Texto Completo: http://repositorio.bc.ufg.br/tede/handle/tede/3426
• topic: Tiossemicarbazonas; MTT; Células de melanoma SK-MEL-37; Apoptose; Thiosemicarbazones; Melanoma cells SK-MEL-37; Apoptosis; BIOQUIMICA::BIOLOGIA MOLECULAR

Melanoma is a type of cancer that arises from melanocytes and is notoriously resistant to radiation and chemotherapy. The thiosemicarbazones are synthetic compounds with marked biological properties such as antibacterial, antiviral, antiprotozoal and antitumor and previous studies have demonstrated cytotoxic activity against the human melanoma cells, so in this study, we evaluated the antiproliferative activity, the enzymatic activity of Caspases 2, 3, 6, 8, 9, the effect on the cell cycle gene expression levels of caspases 2, 3, 6, 8, 9, Apaf-1 and microscopic morphological changes in human melanoma cells (SK -MEL-37) twenty one monoterpene derived from natural thiosemicarbazone (-) - camphene: camphene, benzaldehyde, benzophenone, menthone, ethyl pyruvate, p-nitroacetophenone, pchloroacetophenone, p-methoxyacetophenone, p-methylacetophenone, p fluoracetofenona-phidroxiacetofena, furan, 3-methoxy-4-hydroxybenzaldehyde, p-fluorbenzaldehyde, 2- hydroxybenzaldehyde, cinnamic aldehyde, thiophene-2-carboxaldehyde, 1-H-imidazole-4- carboxaldehyde, tiossemicaroazida and six montoterpeno natural R-(+)-limonene: benzaldehyde, thiosemicarbazide, o-nitro, m-nitro, p-nitro, p-hydroxy and p-dimethylamino. The values found for the inhibitory concentration for 50% of cells (IC50) were between 12 μM and 55 μM. The percentage of cells in phase and in phase G0/G1 decreased SG2 / M increased after forty-eight hours of incubation with benzaldehyde thio-camphene, limonene thio-benzaldehyde, m-nitro, p-hydroxy and thiosemicarbazide increased indicating that the growth inhibitory effect might be also due to arrest of cells at S-G2/M phase. We observed increased activity of caspase 3 (m-nitro thio-limonene), 6 (camphene thio-benzaldehyde and p-hydroxy thio-limonene) and 8 (thio-benzaldehyde limonene). Late apoptotic features were detected in 62% of cells treated with benzaldehyde thio-camphene and morphological changes typical of apoptosis were visualized by fluorescence microscopy and scanning electron microscopy (SEM) after treatment with benzaldehyde thio-camphene chosen due to their low IC50 value (12 mM). It was observed gene expression of caspases 2, 3, 6, 8 and Apaf-1 in cells treated with benzaldehyde thio-camphene indicating the participation of these enzymes in the anti-proliferative effect observed. Our results indicate that the thiosemicarbazones derivatives can inhibit proliferation, regulate cell cycle, induce apoptosis of human melanoma cells (SK-MEL-37) and could be an candidate for future preclinical in vivo studies.