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Previous issue date: 2013-05-16 / 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. / O melanoma é um tipo de câncer que surge nos melanócitos e é notoriamente resistente à
radioterapia e quimioterapia. As tiossemicarbazonas são compostos sintéticos com marcantes
propriedades biológicas tais como antibacteriana, antiviral, antiprotozoária e antitumoral e em
estudos anteriores demonstraram ação citotóxica frente à celulas de melanoma humano, por
isso, neste estudo, foi avaliada a atividade anti-proliferativa, a atividade enzimática das
caspases 2, 3, 6, 8, 9, o efeito no ciclo celular, os níveis de expressão gênica das caspases 2, 3,
6, 8, 9, Apaf-1 e as alterações morfológicas por microscopia em células de melanoma humano
(SK-MEL-37) de vinte e uma tiossemicarbazonas derivadas do monoterpeno natural (-)-
canfeno: canfeno, benzaldeído, benzofenona, mentona, etil piruvato, acetofenona, pnitroacetofenona,
p-cloroacetofenona, p-metoxiacetofenona, p-metilacetofenona, pfluoracetofenona,
p-hidroxiacetofena, furano, 3-metóxi-4-hidroxibenzaldeído, pfluorbenzaldeído,
2-hidroxibenzaldeído, aldeído cinâmico, tiofeno-2-carboxialdeído, 1-Himidazol-
4-carboxialdeído, tiossemicaroazida, bem como seis do montoterpeno natural R-(+)-
limoneno: benzaldeído, tiossemicarbazida, o-nitro, m-nitro, p-nitro, p-dimetilamino e phidróxi
. Os valores encontrados para a concentração inibitória para 50% das células (IC50)
situaram-se entre 12 μM e 55 μM. A porcentagem de células na fase G0/G1diminuiu e na fase
SG2/M aumentou após quarenta e oito horas de incubação com o benzaldeído tio-canfeno,
benzaldeído tio-limoneno, m-nitro, p-hidróxi e tiossemicarbazida, indicando que o efeito
antiproliferativo observado pode ser devido a uma interrupção das células na fase SG2/M.
Observou-se uma maior atividade de caspase 3 (m-nitro tio-limoneno), 6 (benzaldeído tiocanfeno
e p-hidróxi tio-limoneno) e 8 (benzaldeído tio-limoneno). Características apoptóticas
tardias foram detectados em 62% das células tratadas com benzaldeído tio-canfeno e as
alterações morfológicas típicas de processo de apoptose foram visualizadas através da
microscopia de fluorescência e de microscopia eletrônica de varredura (MEV) após
tratamento com o benzaldeído tio-canfeno escolhido devido ao seu baixo valor de IC50 (12
μM). Observou-se a expressão gênica das caspases 2, 3, 6, 8 e o apaf-1 nas células tratadas
com benzaldeído tio-canfeno indicando a participação dessas enzimas no efeito
antiproliferativo observado. Os resultados indicam que as tiossemicarbazonas derivadas de
canfeno e limoneno podem inibir a proliferação celular, regular o ciclo celular e induzir
apoptose nas células de melanoma humano (SK-MEL-37), portanto, podem ser considerados
candidatos para futuros ensaios pré-clínico in vivo.
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.bc.ufg.br:tede/3426 |
| Date | 16 May 2013 |
| Creators | Passos, Débora Cristina Silva dos |
| Contributors | Guillo, Lídia Andreu, Oliveira, Cecília Maria Alves de |
| Publisher | Universidade Federal de Goiás, Programa de Pós-graduação em Biologia (ICB), UFG, Brasil, Instituto de Ciências Biológicas - ICB (RG) |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | Portuguese |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis |
| Format | application/pdf |
| Source | reponame:Biblioteca Digital de Teses e Dissertações da UFG, instname:Universidade Federal de Goiás, instacron:UFG |
| Rights | http://creativecommons.org/licenses/by-nc-nd/4.0/, info:eu-repo/semantics/openAccess |
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