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

Detalhes bibliográficos
Ano de defesa: 2013
Autor(a) principal: Passos, Débora Cristina Silva dos lattes
Orientador(a): Guillo, Lídia Andreu lattes
Banca de defesa: Não Informado pela instituição
Tipo de documento: Tese
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade Federal de Goiás
Programa de Pós-Graduação: Programa de Pós-graduação em Biologia (ICB)
Departamento: Instituto de Ciências Biológicas - ICB (RG)
País: Brasil
Palavras-chave em Português:
Tiossemicarbazonas
MTT
Células de melanoma SK-MEL-37
Apoptose
Palavras-chave em Inglês:
Thiosemicarbazones
Melanoma cells SK-MEL-37
Apoptosis
Área do conhecimento CNPq:
BIOQUIMICA::BIOLOGIA MOLECULAR
Link de acesso: http://repositorio.bc.ufg.br/tede/handle/tede/3426
Resumo: 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.
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spelling Guillo, Lídia Andreuhttp://lattes.cnpq.br/3401436781775091Oliveira, Cecília Maria Alves dehttp://lattes.cnpq.br/4016484271674921Passos, Débora Cristina Silva dos2014-10-22T19:00:24Z2013-05-16PASSOS, Débora Cristina Silva dos. Ação biológica in vitro de tiossemicarbazonas derivadas de canfeno e limoneno em células de melanoma humano (SK-MEL-37). 2013. 84 f. Tese (Doutorado em Biologia) - Universidade Federal de Goiás, Goiânia, 2013.http://repositorio.bc.ufg.br/tede/handle/tede/3426Melanoma 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.Submitted by Erika Demachki (erikademachki@gmail.com) on 2014-10-22T16:44:26Z No. of bitstreams: 4 Tese - Débora Cristina Silva dos Passos - 2013 - Parte 01.pdf: 10357491 bytes, checksum: 1678b4aad93bca319ee5ddb93d3808bc (MD5) Tese - Débora Cristina Silva dos Passos - 2013 - Parte 02.pdf: 9533486 bytes, checksum: ad5e21870e09f4f46a3045a69996aed3 (MD5) Tese - Débora Cristina Silva dos Passos - 2013 - Parte 03.pdf: 8695341 bytes, checksum: 5f8d696c0a73f923cb129f3c0aa1e4b7 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5)Approved for entry into archive by Jaqueline Silva (jtas29@gmail.com) on 2014-10-22T19:00:24Z (GMT) No. of bitstreams: 4 Tese - Débora Cristina Silva dos Passos - 2013 - Parte 01.pdf: 10357491 bytes, checksum: 1678b4aad93bca319ee5ddb93d3808bc (MD5) Tese - Débora Cristina Silva dos Passos - 2013 - Parte 02.pdf: 9533486 bytes, checksum: ad5e21870e09f4f46a3045a69996aed3 (MD5) Tese - Débora Cristina Silva dos Passos - 2013 - Parte 03.pdf: 8695341 bytes, checksum: 5f8d696c0a73f923cb129f3c0aa1e4b7 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5)Made available in DSpace on 2014-10-22T19:00:24Z (GMT). No. of bitstreams: 4 Tese - Débora Cristina Silva dos Passos - 2013 - Parte 01.pdf: 10357491 bytes, checksum: 1678b4aad93bca319ee5ddb93d3808bc (MD5) Tese - Débora Cristina Silva dos Passos - 2013 - Parte 02.pdf: 9533486 bytes, checksum: ad5e21870e09f4f46a3045a69996aed3 (MD5) Tese - Débora Cristina Silva dos Passos - 2013 - Parte 03.pdf: 8695341 bytes, checksum: 5f8d696c0a73f923cb129f3c0aa1e4b7 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2013-05-16application/pdfhttp://repositorio.bc.ufg.br/tede/retrieve/10878/Tese%20-%20D%c3%a9bora%20Cristina%20Silva%20dos%20Passos%20-%202013%20-%20Parte%2001.pdf.jpghttp://repositorio.bc.ufg.br/tede/retrieve/10880/Tese%20-%20D%c3%a9bora%20Cristina%20Silva%20dos%20Passos%20-%202013%20-%20Parte%2002.pdf.jpghttp://repositorio.bc.ufg.br/tede/retrieve/10882/Tese%20-%20D%c3%a9bora%20Cristina%20Silva%20dos%20Passos%20-%202013%20-%20Parte%2003.pdf.jpgporUniversidade Federal de GoiásPrograma de Pós-graduação em Biologia (ICB)UFGBrasilInstituto de Ciências Biológicas - ICB (RG)AFRASIABI, Z.; SINN, E.; CHEN, J.; MA, Y.; RHEINGOLD, A.L.; ZAKHAROV, L.N.; RATH, N. & PAHYDE, S. 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dc.title.por.fl_str_mv Ação biológica in vitro de tiossemicarbazonas derivadas de canfeno e limoneno em células de melanoma humano (SK-MEL-37)
title Ação biológica in vitro de tiossemicarbazonas derivadas de canfeno e limoneno em células de melanoma humano (SK-MEL-37)
spellingShingle Ação biológica in vitro de tiossemicarbazonas derivadas de canfeno e limoneno em células de melanoma humano (SK-MEL-37)
Passos, Débora Cristina Silva dos
Tiossemicarbazonas
MTT
Células de melanoma SK-MEL-37
Apoptose
Thiosemicarbazones
Melanoma cells SK-MEL-37
Apoptosis
BIOQUIMICA::BIOLOGIA MOLECULAR
title_short Ação biológica in vitro de tiossemicarbazonas derivadas de canfeno e limoneno em células de melanoma humano (SK-MEL-37)
title_full Ação biológica in vitro de tiossemicarbazonas derivadas de canfeno e limoneno em células de melanoma humano (SK-MEL-37)
title_fullStr Ação biológica in vitro de tiossemicarbazonas derivadas de canfeno e limoneno em células de melanoma humano (SK-MEL-37)
title_full_unstemmed Ação biológica in vitro de tiossemicarbazonas derivadas de canfeno e limoneno em células de melanoma humano (SK-MEL-37)
title_sort Ação biológica in vitro de tiossemicarbazonas derivadas de canfeno e limoneno em células de melanoma humano (SK-MEL-37)
author Passos, Débora Cristina Silva dos
author_facet Passos, Débora Cristina Silva dos
author_role author
dc.contributor.advisor1.fl_str_mv Guillo, Lídia Andreu
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/3401436781775091
dc.contributor.advisor-co1.fl_str_mv Oliveira, Cecília Maria Alves de
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/4016484271674921
dc.contributor.author.fl_str_mv Passos, Débora Cristina Silva dos
contributor_str_mv Guillo, Lídia Andreu
Oliveira, Cecília Maria Alves de
dc.subject.por.fl_str_mv Tiossemicarbazonas
MTT
Células de melanoma SK-MEL-37
Apoptose
topic Tiossemicarbazonas
MTT
Células de melanoma SK-MEL-37
Apoptose
Thiosemicarbazones
Melanoma cells SK-MEL-37
Apoptosis
BIOQUIMICA::BIOLOGIA MOLECULAR
dc.subject.eng.fl_str_mv Thiosemicarbazones
Melanoma cells SK-MEL-37
Apoptosis
dc.subject.cnpq.fl_str_mv BIOQUIMICA::BIOLOGIA MOLECULAR
description 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.
publishDate 2013
dc.date.issued.fl_str_mv 2013-05-16
dc.date.accessioned.fl_str_mv 2014-10-22T19:00:24Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
status_str publishedVersion
dc.identifier.citation.fl_str_mv PASSOS, Débora Cristina Silva dos. Ação biológica in vitro de tiossemicarbazonas derivadas de canfeno e limoneno em células de melanoma humano (SK-MEL-37). 2013. 84 f. Tese (Doutorado em Biologia) - Universidade Federal de Goiás, Goiânia, 2013.
dc.identifier.uri.fl_str_mv http://repositorio.bc.ufg.br/tede/handle/tede/3426
identifier_str_mv PASSOS, Débora Cristina Silva dos. Ação biológica in vitro de tiossemicarbazonas derivadas de canfeno e limoneno em células de melanoma humano (SK-MEL-37). 2013. 84 f. Tese (Doutorado em Biologia) - Universidade Federal de Goiás, Goiânia, 2013.
url http://repositorio.bc.ufg.br/tede/handle/tede/3426
dc.language.iso.fl_str_mv por
language por
dc.relation.program.fl_str_mv 6883982777473437920
dc.relation.confidence.fl_str_mv 600
600
600
dc.relation.department.fl_str_mv -3872772117827373404
dc.relation.cnpq.fl_str_mv 3962143990328052072
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