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Campo DC | Valor | Idioma |
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dc.contributor.author | Oliveira, Regiane Costa de | - |
dc.date.available | 2022-08-10 | - |
dc.date.available | 2022-08-11T16:57:27Z | - |
dc.date.issued | 2020-07-10 | - |
dc.identifier.uri | http://repositorioinstitucional.uea.edu.br//handle/riuea/4121 | - |
dc.description.abstract | Hematological neoplasms are a heterogeneous group of diseases originating in the bone marrow that present as main tumors of lymphoid and hematopoietic tissues leukemias, lymphomas and myelomas. The main current treatments include chemotherapy and radiation therapy. However, most of these treatments are expensive and result in intense side effects for patients, which demands new safer and more cost-effective therapeutic alternatives. The purpose of this study was to investigate the in vitro anticancer and imunomodulatory activities of natural and semi-synthetic compounds against hematological neoplasms. As human normal peripheral blood mononucleated cells (PBMC) was used in the assays, this project was duly approved by the Research Ethics Committee (CEP) of the HEMOAM Foundation, according to the guidelines recommended by the resolution 466/2012 of the Ministry of Health. First, PBMC and Vero cells were treated with different concentrations of the following compounds: Br- Ell-S03Na, pyrazoloisoquinoline, Z1 and Z2. The cytotoxicity was assessed using the K562, HL-60 and U937 cell lines. All substances tested showed anticancer activity, without significant cytotoxic effect against non-cancerous cells. The substance that showed the best anticancer activity was a derivative of zerumbone (Z1) that had an IC50 value of 5.20μM in HL-60 cells. Regarding the cell cycle, it was observed that the substances Z1 and pyrazoloisoquinoline induced greater capture of cells in the G1 phase of the cell cycle, while in relation to the substance Br-Ell-S03Na and Z2, a higher proportion of capture was observed in the S and G2 phases, respectively. The substances Br-Ell-S03Na and pyrazoloisoquinoline induced the expression of IL-6, but inhibited the expression of IL-8. The Z2 substance also inhibited the expression of IL-8. The results presented by this study demonstrate that the analyzed substances have an important anticancer and immunomodulatory potential, which make them possible candidates to be explored in prospective in vivo studies | pt_BR |
dc.language | por | pt_BR |
dc.publisher | Universidade do Estado do Amazonas | pt_BR |
dc.rights | Acesso Aberto | pt_BR |
dc.subject | Fitoterápicos | pt_BR |
dc.subject | Leucemias | pt_BR |
dc.subject | Neoplasias | pt_BR |
dc.subject | Bioprospecção | pt_BR |
dc.title | Avaliação in vitro da atividade anticancerígena de compostos naturais e semissintéticos contra neoplasias hematológicas | pt_BR |
dc.title.alternative | In vitro evaluation of the anticancer activity of natural and semi-synthetic compounds against hematological neoplasms | pt_BR |
dc.type | Dissertação | pt_BR |
dc.date.accessioned | 2022-08-11T16:57:27Z | - |
dc.contributor.advisor1 | Pontes, Gemilson Soares | - |
dc.contributor.advisor1Lattes | http://lattes.cnpq.br/9081671233815990 | pt_BR |
dc.contributor.referee1 | Costa, Allysom Guimarães da | - |
dc.contributor.referee1Lattes | http://lattes.cnpq.br/7531662673281014 | pt_BR |
dc.contributor.referee2 | Sartim, Marco Aurélio | - |
dc.contributor.referee2Lattes | http://lattes.cnpq.br/0196692401515816 | pt_BR |
dc.contributor.referee3 | Campos, Ceci Sales | - |
dc.contributor.referee3Lattes | http://lattes.cnpq.br/9752987836124768 | pt_BR |
dc.creator.Lattes | http://lattes.cnpq.br/2804370054665763 | pt_BR |
dc.description.resumo | As neoplasias hematológicas são um grupo heterogêneo de doenças originadas na medula óssea que apresentam como principais tumores de tecidos linfoides e hematopoiéticos as leucemias, linfomas e mielomas. Os principais tratamentos atuais incluem quimioterápicos e radioterapia. Contudo, a maioria destes tratamentos é de alto custo e resulta em intensos efeitos colaterais aos pacientes, o que demanda novas alternativas terapêuticas mais seguras e de melhor custo-benefício. Este estudo teve como objetivo principal investigar a atividade anticancerígena e imunomoduladora in vitro de compostos naturais e semissintéticos contra neoplasias hematológicas. Como foram utilizadas células mononucleadas normais do sangue periférico (PBMC) humanas, este projeto foi devidamente aprovado pelo Comitê de Ética em Pesquisa (CEP) da Fundação HEMOAM, de acordo com as diretrizes preconizadas pela resolução 466/2012 do Ministério da Saúde. Primeiramente, PBMC e células Vero foram tratadas com diferentes concentrações dos seguintes compostos: Br-Ell-S03Na, pirazoloisoquinolina, Z1 e Z2. A avaliação da citotoxicidade foi realizada por meio do teste MTT. Em seguida, foi investigada as atividades anticancerígena e imunomoduladora utilizando-se as linhagens celulares K562, HL-60 e U937.Todas as substâncias testadas apresentaram atividade anticancerígena, sem efeito citotóxico significativo contra células não cancerígenas. A substância que apresentou melhor atividade anticancerígena foi um derivado de zerumbona (Z1) que apresentou valor de IC50 de 5.20μM em células HL-60. Em relação ao ciclo celular, foi observado que as substâncias Z1 e pirazoloisoquinolina induziram maior captura na fase G1 do ciclo celular, enquanto que as substâncias Br-Ell-S03Na e Z2 foi observado uma maior a proporção de captura na fase S e G2, respectivamente. As substâncias Br-Ell-S03Na e pirazoloisoquinolina induziram a expressão de IL-6, porém inibiram a expressão de IL- 8. A substancia Z2 também inibiu a expressão de IL-8. Os resultados apresentados por este estudo demonstram que as substâncias analisadas apresentam importante potencial anticancerígeno e imunomodulador, os que as tornam possíveis candidatas para serem exploradas em estudos prospectivos in vivo | pt_BR |
dc.publisher.country | Brasil | pt_BR |
dc.publisher.program | PPGH -PROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS APLICADAS À HEMATOLOGIA | pt_BR |
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