Atividade antitumoral de terpenos e mecanismo de ação do limoneno em células tumorais: uma revisão de patentes, revisão sistemática e meta-análise

Detalhes bibliográficos
Autor(a) principal: Braz, Juliana de Vasconcelos Cerqueira
Data de Publicação: 2020
Tipo de documento: Tese
Idioma: por
Título da fonte: Repositório Institucional da UFS
Texto Completo: http://ri.ufs.br/jspui/handle/riufs/16873
Resumo: Cancer is a complex disease of multifactorial cause, considered a major public health problem by the World Health Organization (WHO). One of the main causes of morbidity and mortality worldwide. Although treatments have evolved significantly, there is still a constant search for more effective drugs. An important source is Natural Products (PN). An example of this, terpenes demonstrate biological activity against cancer, acting during early tumorigenesis, late carcinogenic stages, invasion phase and metastasis. A terpene that is quite abundant in nature and has demonstrated anticancer activity in in vivo and in vitro studies was limonene. However, the mechanisms of limonene's antitumor activity are not fully understood. The aim of the present study is, therefore, to evaluate the antitumor activity of terpenes and the mechanism of action of limonene in tumor cells. To assess the development of terpenes for antitumor activity, a search for terpene patents or terpene formulations was carried out in specialized databases of the World Intellectual Property Organization (WIPO) and Espacenet. Of the total of the seven patents included in the review, China and Japan were the countries that filed the most, three of them were filed by industry and only one is commercialized. Although there is great scientific interest in terpenes, the industry has invested little in this class of natural cancer products. A systematic review with meta-analysis was used to assess the mechanism of action of limonene in tumor cells through a comprehensive systematic search using the Scopus, MEDLINE-PubMed, Web of Science and Science Direct databases, using the descriptors: "limonene "," cancer "," neoplasm "," tumor ". The risk of bias was assessed and considered high, according to the Risk of Bias tool from SYRCLE (RoB). The mechanism of action used by limonene seems to be the induction of cells to apoptosis mainly by the mitochondrial pathway, and can also activate by other signaling pathways. The meta-analysis suggests that limonene acts mainly in apoptosis induced by tumor regression and is therefore a promising natural product for use in the treatment of various types of cancer.
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spelling Braz, Juliana de Vasconcelos CerqueiraSefarini, Mairim Russo2022-12-05T17:37:57Z2022-12-05T17:37:57Z2020BRAZ, Juliana de Vasconcelos Cerqueira. Atividade antitumoral de terpenos e mecanismo de ação do limoneno em células tumorais: uma revisão de patentes, revisão sistemática e meta-análise. 2020. 69 f. Tese (doutorado em Ciências da Saúde) – Universidade Federal de Sergipe, Aracaju, 2020.http://ri.ufs.br/jspui/handle/riufs/16873Cancer is a complex disease of multifactorial cause, considered a major public health problem by the World Health Organization (WHO). One of the main causes of morbidity and mortality worldwide. Although treatments have evolved significantly, there is still a constant search for more effective drugs. An important source is Natural Products (PN). An example of this, terpenes demonstrate biological activity against cancer, acting during early tumorigenesis, late carcinogenic stages, invasion phase and metastasis. A terpene that is quite abundant in nature and has demonstrated anticancer activity in in vivo and in vitro studies was limonene. However, the mechanisms of limonene's antitumor activity are not fully understood. The aim of the present study is, therefore, to evaluate the antitumor activity of terpenes and the mechanism of action of limonene in tumor cells. To assess the development of terpenes for antitumor activity, a search for terpene patents or terpene formulations was carried out in specialized databases of the World Intellectual Property Organization (WIPO) and Espacenet. Of the total of the seven patents included in the review, China and Japan were the countries that filed the most, three of them were filed by industry and only one is commercialized. Although there is great scientific interest in terpenes, the industry has invested little in this class of natural cancer products. A systematic review with meta-analysis was used to assess the mechanism of action of limonene in tumor cells through a comprehensive systematic search using the Scopus, MEDLINE-PubMed, Web of Science and Science Direct databases, using the descriptors: "limonene "," cancer "," neoplasm "," tumor ". The risk of bias was assessed and considered high, according to the Risk of Bias tool from SYRCLE (RoB). The mechanism of action used by limonene seems to be the induction of cells to apoptosis mainly by the mitochondrial pathway, and can also activate by other signaling pathways. The meta-analysis suggests that limonene acts mainly in apoptosis induced by tumor regression and is therefore a promising natural product for use in the treatment of various types of cancer.O câncer é uma doença complexa de causa multifatorial, considerado um grande problema de saúde pública pela Organização Mundial da Saúde (OMS), uma das principais causas de morbimortalidade em todo o mundo. Embora os tratamentos tenham evoluído significativamente, ainda existe uma busca constante por medicamentos mais eficazes. Diante disto, uma fonte importante para desenvolvimento de medicamentos são os Produtos Naturais (PN). A exemplo disto são os terpenos que demonstram atividade biológica contra o câncer, atuando durante a tumorigênese precoce, estágios carcinogênicos tardios, fase de invasão e metástase. Um terpeno bastante abundante na natureza e que demonstrou atividade anticâncer em estudos in vivo e in vitro foi o limoneno. No entanto, os mecanismos da atividade antitumoral do limoneno não são totalmente compreendidos. Assim, o objetivo do presente estudo é realizar uma revisão sistemática, metanálise da literatura e prospecção de patentes para avaliar a atividade antitumoral de terpenos e mecanismo de ação do limoneno. Para avaliar o desenvolvimento dos terpenos para atividade antitumoral, foi realizada uma busca de patentes de terpenos ou formulações a base de terpenos em bancos de dados especializados da Organização Mundial da Propriedade Intelectual (OMPI) e Espacenet. Em paralelo uma revisão sistemática com meta-analise foi realizada para avaliar o mecanismo de ação do limoneno em células tumorais. Os resultados da revisão de patentes indicam a China e o Japão como os países que mais depositaram patentes de terpenos, três delas foram depositadas por indústria e apenas uma é comercializada. Embora exista grande interesse científico pelos terpenos, a indústria pouco tem investido nesta classe de produtos naturais para o câncer. Já a revisão sistemática indica que o mecanismo de ação utilizado pelo limoneno parece ser a indunção de células à apoptose principalmente pela via mitocondrial, podendo também ativar outras vias de sinalização para apoptose. E a metanálise sugere que o limoneno atua principalmente na apoptose induzida pela regressão tumoral sendo, portanto, um produto natural promissor para uso no tratamento de vários tipos de câncer.AracajuporCâncerLimonenoNeoplasiaAtividade antitumoralRevisão de patentesRevisão sistemáticaMetanáliseCancerLimoneneNeoplasmAntitumoral activityPatent reviewSystematic reviewMetanalysisCIENCIAS DA SAUDEAtividade antitumoral de terpenos e mecanismo de ação do limoneno em células tumorais: uma revisão de patentes, revisão sistemática e meta-análiseAntitumor activity of terpenes and mechanism of action of limonene in tumor cells: a patent review, systematic review and meta-analysisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisPós-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/16873/1/license.txt098cbbf65c2c15e1fb2e49c5d306a44cMD51ORIGINALJULIANA_VASCONCELOS_CERQUEIRA_BRAZ.pdfJULIANA_VASCONCELOS_CERQUEIRA_BRAZ.pdfapplication/pdf925265https://ri.ufs.br/jspui/bitstream/riufs/16873/2/JULIANA_VASCONCELOS_CERQUEIRA_BRAZ.pdf61b810becaec62428f254b9f466180b5MD52TEXTJULIANA_VASCONCELOS_CERQUEIRA_BRAZ.pdf.txtJULIANA_VASCONCELOS_CERQUEIRA_BRAZ.pdf.txtExtracted texttext/plain122925https://ri.ufs.br/jspui/bitstream/riufs/16873/3/JULIANA_VASCONCELOS_CERQUEIRA_BRAZ.pdf.txt8c3c9f08c1088f59eef161e311dcc328MD53THUMBNAILJULIANA_VASCONCELOS_CERQUEIRA_BRAZ.pdf.jpgJULIANA_VASCONCELOS_CERQUEIRA_BRAZ.pdf.jpgGenerated Thumbnailimage/jpeg1229https://ri.ufs.br/jspui/bitstream/riufs/16873/4/JULIANA_VASCONCELOS_CERQUEIRA_BRAZ.pdf.jpgb1b395e00c0849ee32fd7fe1033e1405MD54riufs/168732022-12-05 14:37:57.453oai:ufs.br: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Repositório InstitucionalPUBhttps://ri.ufs.br/oai/requestrepositorio@academico.ufs.bropendoar:2022-12-05T17:37:57Repositório Institucional da UFS - Universidade Federal de Sergipe (UFS)false
dc.title.pt_BR.fl_str_mv Atividade antitumoral de terpenos e mecanismo de ação do limoneno em células tumorais: uma revisão de patentes, revisão sistemática e meta-análise
dc.title.alternative.eng.fl_str_mv Antitumor activity of terpenes and mechanism of action of limonene in tumor cells: a patent review, systematic review and meta-analysis
title Atividade antitumoral de terpenos e mecanismo de ação do limoneno em células tumorais: uma revisão de patentes, revisão sistemática e meta-análise
spellingShingle Atividade antitumoral de terpenos e mecanismo de ação do limoneno em células tumorais: uma revisão de patentes, revisão sistemática e meta-análise
Braz, Juliana de Vasconcelos Cerqueira
Câncer
Limoneno
Neoplasia
Atividade antitumoral
Revisão de patentes
Revisão sistemática
Metanálise
Cancer
Limonene
Neoplasm
Antitumoral activity
Patent review
Systematic review
Metanalysis
CIENCIAS DA SAUDE
title_short Atividade antitumoral de terpenos e mecanismo de ação do limoneno em células tumorais: uma revisão de patentes, revisão sistemática e meta-análise
title_full Atividade antitumoral de terpenos e mecanismo de ação do limoneno em células tumorais: uma revisão de patentes, revisão sistemática e meta-análise
title_fullStr Atividade antitumoral de terpenos e mecanismo de ação do limoneno em células tumorais: uma revisão de patentes, revisão sistemática e meta-análise
title_full_unstemmed Atividade antitumoral de terpenos e mecanismo de ação do limoneno em células tumorais: uma revisão de patentes, revisão sistemática e meta-análise
title_sort Atividade antitumoral de terpenos e mecanismo de ação do limoneno em células tumorais: uma revisão de patentes, revisão sistemática e meta-análise
author Braz, Juliana de Vasconcelos Cerqueira
author_facet Braz, Juliana de Vasconcelos Cerqueira
author_role author
dc.contributor.author.fl_str_mv Braz, Juliana de Vasconcelos Cerqueira
dc.contributor.advisor1.fl_str_mv Sefarini, Mairim Russo
contributor_str_mv Sefarini, Mairim Russo
dc.subject.por.fl_str_mv Câncer
Limoneno
Neoplasia
Atividade antitumoral
Revisão de patentes
Revisão sistemática
Metanálise
topic Câncer
Limoneno
Neoplasia
Atividade antitumoral
Revisão de patentes
Revisão sistemática
Metanálise
Cancer
Limonene
Neoplasm
Antitumoral activity
Patent review
Systematic review
Metanalysis
CIENCIAS DA SAUDE
dc.subject.eng.fl_str_mv Cancer
Limonene
Neoplasm
Antitumoral activity
Patent review
Systematic review
Metanalysis
dc.subject.cnpq.fl_str_mv CIENCIAS DA SAUDE
description Cancer is a complex disease of multifactorial cause, considered a major public health problem by the World Health Organization (WHO). One of the main causes of morbidity and mortality worldwide. Although treatments have evolved significantly, there is still a constant search for more effective drugs. An important source is Natural Products (PN). An example of this, terpenes demonstrate biological activity against cancer, acting during early tumorigenesis, late carcinogenic stages, invasion phase and metastasis. A terpene that is quite abundant in nature and has demonstrated anticancer activity in in vivo and in vitro studies was limonene. However, the mechanisms of limonene's antitumor activity are not fully understood. The aim of the present study is, therefore, to evaluate the antitumor activity of terpenes and the mechanism of action of limonene in tumor cells. To assess the development of terpenes for antitumor activity, a search for terpene patents or terpene formulations was carried out in specialized databases of the World Intellectual Property Organization (WIPO) and Espacenet. Of the total of the seven patents included in the review, China and Japan were the countries that filed the most, three of them were filed by industry and only one is commercialized. Although there is great scientific interest in terpenes, the industry has invested little in this class of natural cancer products. A systematic review with meta-analysis was used to assess the mechanism of action of limonene in tumor cells through a comprehensive systematic search using the Scopus, MEDLINE-PubMed, Web of Science and Science Direct databases, using the descriptors: "limonene "," cancer "," neoplasm "," tumor ". The risk of bias was assessed and considered high, according to the Risk of Bias tool from SYRCLE (RoB). The mechanism of action used by limonene seems to be the induction of cells to apoptosis mainly by the mitochondrial pathway, and can also activate by other signaling pathways. The meta-analysis suggests that limonene acts mainly in apoptosis induced by tumor regression and is therefore a promising natural product for use in the treatment of various types of cancer.
publishDate 2020
dc.date.issued.fl_str_mv 2020
dc.date.accessioned.fl_str_mv 2022-12-05T17:37:57Z
dc.date.available.fl_str_mv 2022-12-05T17:37:57Z
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dc.identifier.citation.fl_str_mv BRAZ, Juliana de Vasconcelos Cerqueira. Atividade antitumoral de terpenos e mecanismo de ação do limoneno em células tumorais: uma revisão de patentes, revisão sistemática e meta-análise. 2020. 69 f. Tese (doutorado em Ciências da Saúde) – Universidade Federal de Sergipe, Aracaju, 2020.
dc.identifier.uri.fl_str_mv http://ri.ufs.br/jspui/handle/riufs/16873
identifier_str_mv BRAZ, Juliana de Vasconcelos Cerqueira. Atividade antitumoral de terpenos e mecanismo de ação do limoneno em células tumorais: uma revisão de patentes, revisão sistemática e meta-análise. 2020. 69 f. Tese (doutorado em Ciências da Saúde) – Universidade Federal de Sergipe, Aracaju, 2020.
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