POTENCIAL EFEITO ANTICARCINOGÊNICO E NA ATIVIDADE QUIMIOTERÁPICA IN VITRO DO EXTRATO DE CACAU (Theobroma cacao L.) EM CÉLULAS DE LEUCEMIA MIELOCÍTICA CRÔNICA (K562)
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Repositório Institucional Universidade Franciscana |
Texto Completo: | http://www.tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/1048 |
Resumo: | Chronic myeloid leukemia (CML) is a myeloproliferative disorder altered by neoplastic transformation of the hematopoietic stem cell and the pathognomonic presence of the Philadelphia chromosome (Ph), resulting from a reciprocal translocation between chromosomes 9 and 22. The best therapeutic treatment used for CLM involves the target-molecular chemotherapy with all-trans-retinoic acid (ATRA) and arsenic trioxide. However, beyond some patients being resistant to the treatments, some drugs can also cause damage to healthy cells, that have frequent growth, which contributes to side effects. Therefore, new therapeutic alternatives must be revealed. Thus, studies are looking for new antitumor agents that can help against these possible side effects and drug resistance, to obtain the best results, mainly through natural compounds. In this context, cocoa (Theobroma cacao L.) is included, a fruit used for centuries in the production of chocolate. Moreover, this functional food is also being widely explored for its medicinal action, since it has several bioactive molecules in its chemical matrix, which guarantee important biological properties, such as antiinflammatory, antioxidant, and antitumor. In this scenario, the aim of this study was to investigate whether cocoa extract (Theobroma cacao L.) would have an in vitro anticarcinogenic effect and in chemotherapeutic activity in CML cells (K562). For this, K562 cells were exposed to different concentrations of aqueous cocoa extract (30; 100; 500; 750; 1000; 1500 and 2000 μg/mL) during 24 and 72 hours of incubation. In addition, the effect of cocoa extract was analyzed associated with chemotherapeutics ATRA (1 μM) and arsenic trioxide (250 μg/mL). After the incubation periods, assays were performed to measure the levels of cell viability and proliferation as well as oxidative stress. In addition, the fibroblast line (HFF-1) was exposed to the same concentrations of cocoa extract used for the treatment of K562, in order to identify a possible cytotoxic effect. The results found in this study revealed that the cocoa extract was able to decrease the viability levels of K562 cells exposed to the highest concentrations (1000, 1500 and 2000 μg/mL) during 24 hours of incubation, although for 72 hours of exposure the extract cocoa reduced the levels of cell proliferation in all tested concentration. The anticarcinogenic mechanism of cocoa can be explained by the production of oxidative stress, generated by the increase in the levels of total ROS, nitric oxide and superoxide. In addition, cocoa increased the action of chemotherapy, by reducing cell viability and proliferation. Additionally, cocoa had a selective cytotoxic effect, since the extract did not cause damage to fibroblasts in any tested concentration. Therefore, cocoa has a cytotoxic effect on K562 cells and improves the chemotherapeutic action, without affecting normal cells, highlighting cocoa as a potent anticarcinogenic agent, which has a great potential to be used for therapies with no side effects for CML. |
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Cadoná, Francine CarlaRossoni, CarinaPeroza, Luis RicardoCadoná, Francine CarlaLopes, Aline Costa2022-02-10T19:24:42Z2021-07-16Lopes, Aline Costa. POTENCIAL EFEITO ANTICARCINOGÊNICO E NA ATIVIDADE QUIMIOTERÁPICA IN VITRO DO EXTRATO DE CACAU (Theobroma cacao L.) EM CÉLULAS DE LEUCEMIA MIELOCÍTICA CRÔNICA (K562). 2021. 53f. Dissertação( Mestrado em Ciências da Saúde e da Vida) - Universidade Franciscana, Santa Maria - RS.http://www.tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/1048Chronic myeloid leukemia (CML) is a myeloproliferative disorder altered by neoplastic transformation of the hematopoietic stem cell and the pathognomonic presence of the Philadelphia chromosome (Ph), resulting from a reciprocal translocation between chromosomes 9 and 22. The best therapeutic treatment used for CLM involves the target-molecular chemotherapy with all-trans-retinoic acid (ATRA) and arsenic trioxide. However, beyond some patients being resistant to the treatments, some drugs can also cause damage to healthy cells, that have frequent growth, which contributes to side effects. Therefore, new therapeutic alternatives must be revealed. Thus, studies are looking for new antitumor agents that can help against these possible side effects and drug resistance, to obtain the best results, mainly through natural compounds. In this context, cocoa (Theobroma cacao L.) is included, a fruit used for centuries in the production of chocolate. Moreover, this functional food is also being widely explored for its medicinal action, since it has several bioactive molecules in its chemical matrix, which guarantee important biological properties, such as antiinflammatory, antioxidant, and antitumor. In this scenario, the aim of this study was to investigate whether cocoa extract (Theobroma cacao L.) would have an in vitro anticarcinogenic effect and in chemotherapeutic activity in CML cells (K562). For this, K562 cells were exposed to different concentrations of aqueous cocoa extract (30; 100; 500; 750; 1000; 1500 and 2000 μg/mL) during 24 and 72 hours of incubation. In addition, the effect of cocoa extract was analyzed associated with chemotherapeutics ATRA (1 μM) and arsenic trioxide (250 μg/mL). After the incubation periods, assays were performed to measure the levels of cell viability and proliferation as well as oxidative stress. In addition, the fibroblast line (HFF-1) was exposed to the same concentrations of cocoa extract used for the treatment of K562, in order to identify a possible cytotoxic effect. The results found in this study revealed that the cocoa extract was able to decrease the viability levels of K562 cells exposed to the highest concentrations (1000, 1500 and 2000 μg/mL) during 24 hours of incubation, although for 72 hours of exposure the extract cocoa reduced the levels of cell proliferation in all tested concentration. The anticarcinogenic mechanism of cocoa can be explained by the production of oxidative stress, generated by the increase in the levels of total ROS, nitric oxide and superoxide. In addition, cocoa increased the action of chemotherapy, by reducing cell viability and proliferation. Additionally, cocoa had a selective cytotoxic effect, since the extract did not cause damage to fibroblasts in any tested concentration. Therefore, cocoa has a cytotoxic effect on K562 cells and improves the chemotherapeutic action, without affecting normal cells, highlighting cocoa as a potent anticarcinogenic agent, which has a great potential to be used for therapies with no side effects for CML.A leucemia mieloide crônica (LMC) é um distúrbio mieloproliferativo caracterizado pela transformação neoplásica da célula-tronco hematopoiética e a presença patognomônica do cromossomo Filadélfia (Ph) decorrente de uma translocação recíproca entre os cromossomos 9 e 22. A principal abordagem terapêutica para LMC envolve a utilização de quimioterapia alvo-molecular com o ácido all-trans-retinóico (ATRA) e trióxido de arsênio. No entanto, além de alguns pacientes apresentarem resistência aos tratamentos, alguns fármacos podem acabar lesionando não somente células neoplásicas, mas também células saudáveis que possuem um crescimento frequente, o que contribui para os efeitos colaterais. Por isso, novas alternativas terapêuticas devem ser reveladas. Dessa forma, busca-se por novos agentes antitumorais que possam auxiliar contra esses possíveis efeitos colaterais e na resistência de fármacos, para obtenção de melhores resultados principalmente através de compostos naturais. Nesse contexto, insere-se o cacau (Theobroma cacao L.), fruto utilizado desde séculos passados na produção de chocolate, mas que também está sendo bastante explorado pela função medicinal, já que apresenta inúmeras moléculas bioativas na sua matriz química, que garantem propriedades biológicas importantes, como anti-inflamatória, antioxidante e antitumoral. Diante desse cenário, o objetivo desse estudo foi investigar se o extrato de cacau (Theobroma cacao L.) teria efeito anticarcigonênico e na atividade quimioterápica in vitro em células de LMC (K562). Para isso, as células K562 foram expostas a diferentes concentrações de extrato aquoso de cacau (30; 100; 500; 750; 1000; 1500 e 2000 μg/mL) durante 24 e 72 horas de incubação. Além disso, o efeito do extrato de cacau foi analisado associado aos quimioterápicos ATRA (1 μM) e trióxido de arsênio (250 μg/mL). Após os períodos de incubação, foram realizados ensaios para mensurar os níveis de viabilidade e proliferação celular e estresse oxidativo. Além disso, a linhagem de fibroblastos (HFF-1) foi exposta as mesmas concentrações do extrato de cacau utilizadas para o tratamento das K562, com vistas a identificar um possível efeito citotóxico. Os resultados encontrados nesse estudo, revelaram que o extrato de cacau foi capaz de diminuir os níveis de viabilidade das células K562 expostas às concentrações maiores (1000; 1500 e 2000 μg/mL) durante 24 horas de incubação, já em 72 horas de exposição o extrato de cacau reduziu os níveis de proliferação celular em todas as concentrações testadas. O mecanismo anticarcinogênico do cacau pode ser explicado por meio da produção do estresse oxidativo, gerado pelo aumento dos níveis de EROs totais, óxido nítrico e superóxido. Além disso, o cacau aumentou a ação da quimioterapia, por meio da redução da viabilidade e proliferação celular. Adicionalmente, o cacau apresentou um efeito citotóxico seletivo, já não causou dados aos fibroblastos em nenhuma concentração utilizada. Portanto, conclui-se que o cacau possui efeito citotóxico para as células K562 e além disso promove uma melhora na ação quimioterápica, sem afetar células normais, destacando o cacau como um potente agente anticarcinogênico, o qual apresenta um grande potencial para ser utilizado para terapias inovadoras, sem efeitos colaterais, para a LMC.Submitted by Clarice Rosa Machado (clarice.machado@ufn.edu.br) on 2022-02-10T19:24:42Z No. of bitstreams: 2 Dissertacao_AlineCostaLopes_SemAssinaturas.pdf: 1236197 bytes, checksum: 6a25e672490a6126ee6a3f566990041d (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Made available in DSpace on 2022-02-10T19:24:42Z (GMT). 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dc.title.por.fl_str_mv |
POTENCIAL EFEITO ANTICARCINOGÊNICO E NA ATIVIDADE QUIMIOTERÁPICA IN VITRO DO EXTRATO DE CACAU (Theobroma cacao L.) EM CÉLULAS DE LEUCEMIA MIELOCÍTICA CRÔNICA (K562) |
title |
POTENCIAL EFEITO ANTICARCINOGÊNICO E NA ATIVIDADE QUIMIOTERÁPICA IN VITRO DO EXTRATO DE CACAU (Theobroma cacao L.) EM CÉLULAS DE LEUCEMIA MIELOCÍTICA CRÔNICA (K562) |
spellingShingle |
POTENCIAL EFEITO ANTICARCINOGÊNICO E NA ATIVIDADE QUIMIOTERÁPICA IN VITRO DO EXTRATO DE CACAU (Theobroma cacao L.) EM CÉLULAS DE LEUCEMIA MIELOCÍTICA CRÔNICA (K562) Lopes, Aline Costa Cacau, Câncer, Resistência Tumoral, Ácido trans-retinóico, Efeito Anticarcinogênico. Cocoa, Cancer, Tumor Resistance, All-trans Retinoic Acid, Anticarcinogenic effect. Ciências da Saúde e da Vida |
title_short |
POTENCIAL EFEITO ANTICARCINOGÊNICO E NA ATIVIDADE QUIMIOTERÁPICA IN VITRO DO EXTRATO DE CACAU (Theobroma cacao L.) EM CÉLULAS DE LEUCEMIA MIELOCÍTICA CRÔNICA (K562) |
title_full |
POTENCIAL EFEITO ANTICARCINOGÊNICO E NA ATIVIDADE QUIMIOTERÁPICA IN VITRO DO EXTRATO DE CACAU (Theobroma cacao L.) EM CÉLULAS DE LEUCEMIA MIELOCÍTICA CRÔNICA (K562) |
title_fullStr |
POTENCIAL EFEITO ANTICARCINOGÊNICO E NA ATIVIDADE QUIMIOTERÁPICA IN VITRO DO EXTRATO DE CACAU (Theobroma cacao L.) EM CÉLULAS DE LEUCEMIA MIELOCÍTICA CRÔNICA (K562) |
title_full_unstemmed |
POTENCIAL EFEITO ANTICARCINOGÊNICO E NA ATIVIDADE QUIMIOTERÁPICA IN VITRO DO EXTRATO DE CACAU (Theobroma cacao L.) EM CÉLULAS DE LEUCEMIA MIELOCÍTICA CRÔNICA (K562) |
title_sort |
POTENCIAL EFEITO ANTICARCINOGÊNICO E NA ATIVIDADE QUIMIOTERÁPICA IN VITRO DO EXTRATO DE CACAU (Theobroma cacao L.) EM CÉLULAS DE LEUCEMIA MIELOCÍTICA CRÔNICA (K562) |
author |
Lopes, Aline Costa |
author_facet |
Lopes, Aline Costa |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Cadoná, Francine Carla |
dc.contributor.referee1.fl_str_mv |
Rossoni, Carina |
dc.contributor.referee2.fl_str_mv |
Peroza, Luis Ricardo |
dc.contributor.referee3.fl_str_mv |
Cadoná, Francine Carla |
dc.contributor.author.fl_str_mv |
Lopes, Aline Costa |
contributor_str_mv |
Cadoná, Francine Carla Rossoni, Carina Peroza, Luis Ricardo Cadoná, Francine Carla |
dc.subject.por.fl_str_mv |
Cacau, Câncer, Resistência Tumoral, Ácido trans-retinóico, Efeito Anticarcinogênico. |
topic |
Cacau, Câncer, Resistência Tumoral, Ácido trans-retinóico, Efeito Anticarcinogênico. Cocoa, Cancer, Tumor Resistance, All-trans Retinoic Acid, Anticarcinogenic effect. Ciências da Saúde e da Vida |
dc.subject.eng.fl_str_mv |
Cocoa, Cancer, Tumor Resistance, All-trans Retinoic Acid, Anticarcinogenic effect. |
dc.subject.cnpq.fl_str_mv |
Ciências da Saúde e da Vida |
description |
Chronic myeloid leukemia (CML) is a myeloproliferative disorder altered by neoplastic transformation of the hematopoietic stem cell and the pathognomonic presence of the Philadelphia chromosome (Ph), resulting from a reciprocal translocation between chromosomes 9 and 22. The best therapeutic treatment used for CLM involves the target-molecular chemotherapy with all-trans-retinoic acid (ATRA) and arsenic trioxide. However, beyond some patients being resistant to the treatments, some drugs can also cause damage to healthy cells, that have frequent growth, which contributes to side effects. Therefore, new therapeutic alternatives must be revealed. Thus, studies are looking for new antitumor agents that can help against these possible side effects and drug resistance, to obtain the best results, mainly through natural compounds. In this context, cocoa (Theobroma cacao L.) is included, a fruit used for centuries in the production of chocolate. Moreover, this functional food is also being widely explored for its medicinal action, since it has several bioactive molecules in its chemical matrix, which guarantee important biological properties, such as antiinflammatory, antioxidant, and antitumor. In this scenario, the aim of this study was to investigate whether cocoa extract (Theobroma cacao L.) would have an in vitro anticarcinogenic effect and in chemotherapeutic activity in CML cells (K562). For this, K562 cells were exposed to different concentrations of aqueous cocoa extract (30; 100; 500; 750; 1000; 1500 and 2000 μg/mL) during 24 and 72 hours of incubation. In addition, the effect of cocoa extract was analyzed associated with chemotherapeutics ATRA (1 μM) and arsenic trioxide (250 μg/mL). After the incubation periods, assays were performed to measure the levels of cell viability and proliferation as well as oxidative stress. In addition, the fibroblast line (HFF-1) was exposed to the same concentrations of cocoa extract used for the treatment of K562, in order to identify a possible cytotoxic effect. The results found in this study revealed that the cocoa extract was able to decrease the viability levels of K562 cells exposed to the highest concentrations (1000, 1500 and 2000 μg/mL) during 24 hours of incubation, although for 72 hours of exposure the extract cocoa reduced the levels of cell proliferation in all tested concentration. The anticarcinogenic mechanism of cocoa can be explained by the production of oxidative stress, generated by the increase in the levels of total ROS, nitric oxide and superoxide. In addition, cocoa increased the action of chemotherapy, by reducing cell viability and proliferation. Additionally, cocoa had a selective cytotoxic effect, since the extract did not cause damage to fibroblasts in any tested concentration. Therefore, cocoa has a cytotoxic effect on K562 cells and improves the chemotherapeutic action, without affecting normal cells, highlighting cocoa as a potent anticarcinogenic agent, which has a great potential to be used for therapies with no side effects for CML. |
publishDate |
2021 |
dc.date.issued.fl_str_mv |
2021-07-16 |
dc.date.accessioned.fl_str_mv |
2022-02-10T19:24:42Z |
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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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publishedVersion |
dc.identifier.citation.fl_str_mv |
Lopes, Aline Costa. POTENCIAL EFEITO ANTICARCINOGÊNICO E NA ATIVIDADE QUIMIOTERÁPICA IN VITRO DO EXTRATO DE CACAU (Theobroma cacao L.) EM CÉLULAS DE LEUCEMIA MIELOCÍTICA CRÔNICA (K562). 2021. 53f. Dissertação( Mestrado em Ciências da Saúde e da Vida) - Universidade Franciscana, Santa Maria - RS. |
dc.identifier.uri.fl_str_mv |
http://www.tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/1048 |
identifier_str_mv |
Lopes, Aline Costa. POTENCIAL EFEITO ANTICARCINOGÊNICO E NA ATIVIDADE QUIMIOTERÁPICA IN VITRO DO EXTRATO DE CACAU (Theobroma cacao L.) EM CÉLULAS DE LEUCEMIA MIELOCÍTICA CRÔNICA (K562). 2021. 53f. Dissertação( Mestrado em Ciências da Saúde e da Vida) - Universidade Franciscana, Santa Maria - RS. |
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http://www.tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/1048 |
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Universidade Franciscana |
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