Efeito antiproliferativo e pró-apoptótico de derivados de lausona em células de melanoma
Ano de defesa: | 2021 |
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Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | |
Tipo de documento: | Dissertação |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Não Informado pela instituição
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Programa de Pós-Graduação: |
Pós-Graduação em Ciências da Saúde
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Departamento: |
Não Informado pela instituição
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País: |
Não Informado pela instituição
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://ri.ufs.br/jspui/handle/riufs/16854 |
Resumo: | Cancer affects millions of people worldwide and is responsible for 8.8 million deaths per year. Among the skin-type cancer, melanoma is the most aggressive and it was responsible for more than 50.000 deaths in 2020. The impact caused by this disease reveals the importance of research for new molecules with more effective antitumor activity. Natural products are an important source of bioactive molecules, and lawsone, naphthoquinone widely studied, is an important source of molecules with cytotoxic activity. In this context, the study aimed to evaluate the cytotoxic effect of galactoside derivative of lausona in melanoma cells. For this, the degree of inhibition of cell proliferation (GI) of 16 lawsone derivatives was evaluated against three tumor cell lines: lung carcinoma (A549), melanoma (B16F10) and glioma (C6), by the Sulforrodamine B assay. Seven compounds (1, 9, 10, 11, 13, 14 and 15) showed a degree of inhibition greater than 75% in the three cells studied. According to the chemical characteristics of molecule 9, such as the presence of triazole ring and galactose, and the low IC50 (5.3 μM) obtained in 72 h of treatment, this molecule was selected for the next tests in the B16F10 cells. The clonogenic assay showed that the molecule reduced the formation of melanoma colonies. In addition, morphological changes of the melanoma lineage were observed by staing with DAPI and Faloidin/FITC. In this analysis, apoptotic changes were evidenced, in addition to cytoplasmic reduction with changes in the disposition of actin fibers, and loss of cellular conformation in relation to control. These results corroborate flow cytometry, in which showed apoptotic (Annexin positive) and necrosis (PI positive) cell were evaluated, with a percentage increase in apoptosis cells after treatment. The results presented in this work reveal an important active potential of compound 9, derived from lawsone, on tumor cells. |
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Franca, Mariana Nobre Farias deCorrêa, Cristiane BaniScher, Ricardo2022-11-30T17:52:12Z2022-11-30T17:52:12Z2021FRANCA, Mariana Nobre Farias de. Efeito antiproliferativo e pró-apoptótico de derivados de lausona em células de melanoma. 2021. 61 f. Dissertação (Mestrado em Ciências da Saúde) - Universidade Federal de Sergipe, Aracaju, 2021.http://ri.ufs.br/jspui/handle/riufs/16854Cancer affects millions of people worldwide and is responsible for 8.8 million deaths per year. Among the skin-type cancer, melanoma is the most aggressive and it was responsible for more than 50.000 deaths in 2020. The impact caused by this disease reveals the importance of research for new molecules with more effective antitumor activity. Natural products are an important source of bioactive molecules, and lawsone, naphthoquinone widely studied, is an important source of molecules with cytotoxic activity. In this context, the study aimed to evaluate the cytotoxic effect of galactoside derivative of lausona in melanoma cells. For this, the degree of inhibition of cell proliferation (GI) of 16 lawsone derivatives was evaluated against three tumor cell lines: lung carcinoma (A549), melanoma (B16F10) and glioma (C6), by the Sulforrodamine B assay. Seven compounds (1, 9, 10, 11, 13, 14 and 15) showed a degree of inhibition greater than 75% in the three cells studied. According to the chemical characteristics of molecule 9, such as the presence of triazole ring and galactose, and the low IC50 (5.3 μM) obtained in 72 h of treatment, this molecule was selected for the next tests in the B16F10 cells. The clonogenic assay showed that the molecule reduced the formation of melanoma colonies. In addition, morphological changes of the melanoma lineage were observed by staing with DAPI and Faloidin/FITC. In this analysis, apoptotic changes were evidenced, in addition to cytoplasmic reduction with changes in the disposition of actin fibers, and loss of cellular conformation in relation to control. These results corroborate flow cytometry, in which showed apoptotic (Annexin positive) and necrosis (PI positive) cell were evaluated, with a percentage increase in apoptosis cells after treatment. The results presented in this work reveal an important active potential of compound 9, derived from lawsone, on tumor cells.O câncer atinge milhões de pessoas no mundo e é responsável por 8,8 milhões de mortes por ano. Dentre os cânceres que acometem a pele, o melanoma é o mais agressivo e foi responsável por mais de 50.000 mortes em 2020. O impacto causado por essa doença revela a importância de pesquisas por novas moléculas com atividade antitumoral mais efetiva. Produtos naturais são uma importante fonte de moléculas bioativas, e a lausona, naftoquinona amplamente estudada, é uma importante fonte de moléculas com atividade citotóxica. Neste contexto, o objetivo desse estudo foi avaliar o efeito citotóxico de derivados de lausona em linhagem de melanoma. Para isso, foi avaliado o grau de inibição da proliferação celular (GI) de 16 moléculas derivadas de lausona frente a três linhagens de células tumorais: carcinoma de pulmão (A549), melanoma (B16F10) e glioma (C6), pelo ensaio de Sulforrodamina B. Sete compostos (1, 9, 10, 11, 13, 14 e 15) apresentaram grau de inibição maior que 75% nas três linhagens estudadas. De acordo com as características químicas da molécula 9, tais como, presença de anel triazol e galactose, e a baixa CI50 (5,3 μM) obtida em 72 h de tratamento, esta molécula foi selecionada para os próximos ensaios na linhagem B16F10. O ensaio clonogênico mostrou que a molécula reduziu a formação de colônias de melanoma. Além disso, foram observadas alterações morfológicas da linhagem de melanoma pela marcação com DAPI e Faloidina/FITC. Nessa análise foi evidenciado alterações características de apoptose, além da redução citoplasmática com alterações na disposição dos filamentos de actina, e perda da conformação celular em relação ao controle. Esses resultados corroboram a citometria de fluxo, na qual foram avaliadas as células em apoptose (Anexina positivas) e necrose (PI positivas), com aumento percentual de células em apoptose após tratamento. Com base nesses resultados, pode-se concluir que o derivado de lausona 9 apresenta um importante potencial citotóxico com atividade mediada por sua característica pró-apoptótica em células de melanoma.AracajuporCiências da saúdeMelanomaCélula tumoralLausonaCitotoxicidadeApoptoseHealth SciencesMelanomaTumor cellLawsonaCytotoxicityApoptosisCIENCIAS DA SAUDEEfeito antiproliferativo e pró-apoptótico de derivados de lausona em células de melanomaAnti-proliferative and pro-apoptotic effect of lawsone derivatives on melanoma cellsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisPós-Graduação em Ciências da SaúdeUniversidade Federal de Sergipereponame:Repositório Institucional da UFSinstname:Universidade Federal de Sergipe (UFS)instacron:UFSinfo:eu-repo/semantics/openAccessLICENSElicense.txtlicense.txttext/plain; charset=utf-81475https://ri.ufs.br/jspui/bitstream/riufs/16854/1/license.txt098cbbf65c2c15e1fb2e49c5d306a44cMD51ORIGINALMARIANA_NOBRE_FARIAS_FRANCA.pdfMARIANA_NOBRE_FARIAS_FRANCA.pdfapplication/pdf21553540https://ri.ufs.br/jspui/bitstream/riufs/16854/2/MARIANA_NOBRE_FARIAS_FRANCA.pdf891fb801729698b59e83a96e4f71e6abMD52TEXTMARIANA_NOBRE_FARIAS_FRANCA.pdf.txtMARIANA_NOBRE_FARIAS_FRANCA.pdf.txtExtracted texttext/plain61https://ri.ufs.br/jspui/bitstream/riufs/16854/3/MARIANA_NOBRE_FARIAS_FRANCA.pdf.txt12e043953cadc5683745a10a5ed85d37MD53THUMBNAILMARIANA_NOBRE_FARIAS_FRANCA.pdf.jpgMARIANA_NOBRE_FARIAS_FRANCA.pdf.jpgGenerated Thumbnailimage/jpeg1205https://ri.ufs.br/jspui/bitstream/riufs/16854/4/MARIANA_NOBRE_FARIAS_FRANCA.pdf.jpg330241fa064795c294c4312489aeb576MD54riufs/168542022-11-30 14:52:12.297oai:ufs.br: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Repositório InstitucionalPUBhttps://ri.ufs.br/oai/requestrepositorio@academico.ufs.bropendoar:2022-11-30T17:52:12Repositório Institucional da UFS - Universidade Federal de Sergipe (UFS)false |
dc.title.pt_BR.fl_str_mv |
Efeito antiproliferativo e pró-apoptótico de derivados de lausona em células de melanoma |
dc.title.alternative.eng.fl_str_mv |
Anti-proliferative and pro-apoptotic effect of lawsone derivatives on melanoma cells |
title |
Efeito antiproliferativo e pró-apoptótico de derivados de lausona em células de melanoma |
spellingShingle |
Efeito antiproliferativo e pró-apoptótico de derivados de lausona em células de melanoma Franca, Mariana Nobre Farias de Ciências da saúde Melanoma Célula tumoral Lausona Citotoxicidade Apoptose Health Sciences Melanoma Tumor cell Lawsona Cytotoxicity Apoptosis CIENCIAS DA SAUDE |
title_short |
Efeito antiproliferativo e pró-apoptótico de derivados de lausona em células de melanoma |
title_full |
Efeito antiproliferativo e pró-apoptótico de derivados de lausona em células de melanoma |
title_fullStr |
Efeito antiproliferativo e pró-apoptótico de derivados de lausona em células de melanoma |
title_full_unstemmed |
Efeito antiproliferativo e pró-apoptótico de derivados de lausona em células de melanoma |
title_sort |
Efeito antiproliferativo e pró-apoptótico de derivados de lausona em células de melanoma |
author |
Franca, Mariana Nobre Farias de |
author_facet |
Franca, Mariana Nobre Farias de |
author_role |
author |
dc.contributor.author.fl_str_mv |
Franca, Mariana Nobre Farias de |
dc.contributor.advisor1.fl_str_mv |
Corrêa, Cristiane Bani |
dc.contributor.advisor-co1.fl_str_mv |
Scher, Ricardo |
contributor_str_mv |
Corrêa, Cristiane Bani Scher, Ricardo |
dc.subject.por.fl_str_mv |
Ciências da saúde Melanoma Célula tumoral Lausona Citotoxicidade Apoptose |
topic |
Ciências da saúde Melanoma Célula tumoral Lausona Citotoxicidade Apoptose Health Sciences Melanoma Tumor cell Lawsona Cytotoxicity Apoptosis CIENCIAS DA SAUDE |
dc.subject.eng.fl_str_mv |
Health Sciences Melanoma Tumor cell Lawsona Cytotoxicity Apoptosis |
dc.subject.cnpq.fl_str_mv |
CIENCIAS DA SAUDE |
description |
Cancer affects millions of people worldwide and is responsible for 8.8 million deaths per year. Among the skin-type cancer, melanoma is the most aggressive and it was responsible for more than 50.000 deaths in 2020. The impact caused by this disease reveals the importance of research for new molecules with more effective antitumor activity. Natural products are an important source of bioactive molecules, and lawsone, naphthoquinone widely studied, is an important source of molecules with cytotoxic activity. In this context, the study aimed to evaluate the cytotoxic effect of galactoside derivative of lausona in melanoma cells. For this, the degree of inhibition of cell proliferation (GI) of 16 lawsone derivatives was evaluated against three tumor cell lines: lung carcinoma (A549), melanoma (B16F10) and glioma (C6), by the Sulforrodamine B assay. Seven compounds (1, 9, 10, 11, 13, 14 and 15) showed a degree of inhibition greater than 75% in the three cells studied. According to the chemical characteristics of molecule 9, such as the presence of triazole ring and galactose, and the low IC50 (5.3 μM) obtained in 72 h of treatment, this molecule was selected for the next tests in the B16F10 cells. The clonogenic assay showed that the molecule reduced the formation of melanoma colonies. In addition, morphological changes of the melanoma lineage were observed by staing with DAPI and Faloidin/FITC. In this analysis, apoptotic changes were evidenced, in addition to cytoplasmic reduction with changes in the disposition of actin fibers, and loss of cellular conformation in relation to control. These results corroborate flow cytometry, in which showed apoptotic (Annexin positive) and necrosis (PI positive) cell were evaluated, with a percentage increase in apoptosis cells after treatment. The results presented in this work reveal an important active potential of compound 9, derived from lawsone, on tumor cells. |
publishDate |
2021 |
dc.date.issued.fl_str_mv |
2021 |
dc.date.accessioned.fl_str_mv |
2022-11-30T17:52:12Z |
dc.date.available.fl_str_mv |
2022-11-30T17:52:12Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/masterThesis |
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masterThesis |
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FRANCA, Mariana Nobre Farias de. Efeito antiproliferativo e pró-apoptótico de derivados de lausona em células de melanoma. 2021. 61 f. Dissertação (Mestrado em Ciências da Saúde) - Universidade Federal de Sergipe, Aracaju, 2021. |
dc.identifier.uri.fl_str_mv |
http://ri.ufs.br/jspui/handle/riufs/16854 |
identifier_str_mv |
FRANCA, Mariana Nobre Farias de. Efeito antiproliferativo e pró-apoptótico de derivados de lausona em células de melanoma. 2021. 61 f. Dissertação (Mestrado em Ciências da Saúde) - Universidade Federal de Sergipe, Aracaju, 2021. |
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Pós-Graduação em Ciências da Saúde |
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Universidade Federal de Sergipe |
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