Eficácia do [10]-gingerol contra metástases de câncer de mama : estudos in vitro e in vivo em camundongos
Autor(a) principal: | |
---|---|
Data de Publicação: | 2015 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFSCAR |
Texto Completo: | https://repositorio.ufscar.br/handle/ufscar/7699 |
Resumo: | Breast cancer is the leading cause of death in Brazil and worldwide, between the types of cancer, triple negative TNBC (Triple Negative Breast Cancer), which do not express hormone receptors, represents 20% of the cases and presents relapses within 3 years. However, the major cause of death in cancer is due the formation of metastasis. The TNBC has a greater propensity to form lung and brain metastasis. Furthermore, currently few treatments are available. Search for new target treatments, with fewer side effects is very important to treat this disease. Natural products are rich sources of molecules with antitumoral activity; among them are the gingerols, from ginger and resveratrol, from grapes. Nevertheless, not much is known about antitumor activity of [10]-gingerol (10G). Therefore, the aim of this work was to investigate the potential use of 10G as an antimetastatic molecule in in vitro and in vivo experiments. In this work, 10G had antiproliferative activity on several breast cancer cell lines (4T1BM2, 4T1BM2 shRNAβ3, 4T1Br4, MDA-MB-231, MDA-MB-231 BrM) and on a normal cell line, bEnd.3. The natural compounds affected tumor cell morphology and RSVT was able to inhibit cell migration and adhesion through vitronectin. 10G induced apoptosis via the extrinsic pathway through the increase of caspase-9, -3 and -7 expression and decrease of Bcl-2 expression, induced cell cycle arrest in G1 and subG0 phase. In in vivo models, 10G inhibited primary tumor growth and lung metastasis, as well as bone and brain metastasis. Therefore, this study was able to provide new data as 10G can be acting in tumor cells and its possible clinical application. |
id |
SCAR_c1973930381497dbf117beb8bc427987 |
---|---|
oai_identifier_str |
oai:repositorio.ufscar.br:ufscar/7699 |
network_acronym_str |
SCAR |
network_name_str |
Repositório Institucional da UFSCAR |
repository_id_str |
4322 |
spelling |
Martin, Ana Carolina Baptista MorenoAraújo, Heloísa Sobreiro Selistre dehttp://lattes.cnpq.br/4065824911933203http://lattes.cnpq.br/0612591885565016ff87b9d8-6283-489e-98e2-a92223d627842016-10-05T13:48:36Z2016-10-05T13:48:36Z2015-03-20MARTIN, Ana Carolina Baptista Moreno. Eficácia do [10]-gingerol contra metástases de câncer de mama : estudos in vitro e in vivo em camundongos. 2015. Tese (Doutorado em Genética Evolutiva e Biologia Molecular) – Universidade Federal de São Carlos, São Carlos, 2015. Disponível em: https://repositorio.ufscar.br/handle/ufscar/7699.https://repositorio.ufscar.br/handle/ufscar/7699Breast cancer is the leading cause of death in Brazil and worldwide, between the types of cancer, triple negative TNBC (Triple Negative Breast Cancer), which do not express hormone receptors, represents 20% of the cases and presents relapses within 3 years. However, the major cause of death in cancer is due the formation of metastasis. The TNBC has a greater propensity to form lung and brain metastasis. Furthermore, currently few treatments are available. Search for new target treatments, with fewer side effects is very important to treat this disease. Natural products are rich sources of molecules with antitumoral activity; among them are the gingerols, from ginger and resveratrol, from grapes. Nevertheless, not much is known about antitumor activity of [10]-gingerol (10G). Therefore, the aim of this work was to investigate the potential use of 10G as an antimetastatic molecule in in vitro and in vivo experiments. In this work, 10G had antiproliferative activity on several breast cancer cell lines (4T1BM2, 4T1BM2 shRNAβ3, 4T1Br4, MDA-MB-231, MDA-MB-231 BrM) and on a normal cell line, bEnd.3. The natural compounds affected tumor cell morphology and RSVT was able to inhibit cell migration and adhesion through vitronectin. 10G induced apoptosis via the extrinsic pathway through the increase of caspase-9, -3 and -7 expression and decrease of Bcl-2 expression, induced cell cycle arrest in G1 and subG0 phase. In in vivo models, 10G inhibited primary tumor growth and lung metastasis, as well as bone and brain metastasis. Therefore, this study was able to provide new data as 10G can be acting in tumor cells and its possible clinical application.O câncer de mama é o que mais afeta as mulheres no Brasil e no mundo, entre os tipos de câncer de mama, o triplo negativo TNBC (Triple Negative Breast Cancer), que não expressa nenhum receptor hormonal, corresponde a 20% dos casos e apresenta recidivas em três anos. Entretanto, a maior causa de morte no câncer é devido a formação de metástases. O TNBC possui uma maior propensão a metástases pulmonares e cerebrais. Além disso, atualmente poucos tratamentos estão disponíveis. Buscas para novos medicamentos alvo para o TNBC e com menos efeitos colaterais são de grande importância para o tratamento dessa doença. Produtos naturais são fontes ricas em moléculas com atividades antitumorais, dentre elas os gingeróis, presentes no gengibre e o resveratrol (RSVT), presente nas uvas. Entretanto, pouco se sabe da atividade antitumoral do [10]-gingerol (10G). Este trabalho teve como objetivo investigar o potencial uso do 10G como molécula antimetastática em experimentos in vitro e in vivo. Neste trabalho verificou-se a atividade antiproliferativa do 10G e do RSVT em diversas linhagens de câncer de mama (4T1BM2, 4T1BM2 shRNAβ3, 4T1Br4, MDA-MB- 231, MDA-MB-231 BrM) e um controle de célula normal, a bEnd.3. Os produtos naturais (PNs) usados afetam a morfologia celular nas células tumorais e o RSVT é capaz de inibir a adesão e migração via vitronectina. O 10G induziu apoptose da linhagem 4T1Br4 através da via extrínseca, com o aumento da expressão de casspase-9, -3 e -7; induziu a parada do ciclo celular nas fases G1 e sub G0. Em modelos de metástase in vivo o 10G inibiu o crescimento do tumor primário e de metástases pulmonares, além de inibir metástases ósseas e cerebrais. Portanto, este trabalho foi capaz de fornecer dados de como o 10G atua nas células tumorais e sua possível aplicação clínica.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)porUniversidade Federal de São CarlosCâmpus São CarlosPrograma de Pós-Graduação em Genética Evolutiva e Biologia Molecular - PPGGEvUFSCarCâncer de mamaGingerolMetástaseCérebroResveratrolMetastasisNatural Product[10]-gingerolBrainCIENCIAS BIOLOGICAS::GENETICACIENCIAS DA SAUDEEficácia do [10]-gingerol contra metástases de câncer de mama : estudos in vitro e in vivo em camundongosinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisOnline600600b61211db-d955-45b7-886e-a0cefb89980finfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFSCARinstname:Universidade Federal de São Carlos (UFSCAR)instacron:UFSCARORIGINALTeseACBMM.pdfTeseACBMM.pdfapplication/pdf12490231https://repositorio.ufscar.br/bitstream/ufscar/7699/1/TeseACBMM.pdf097b90957f143d8d696733602a92d242MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81957https://repositorio.ufscar.br/bitstream/ufscar/7699/2/license.txtae0398b6f8b235e40ad82cba6c50031dMD52TEXTTeseACBMM.pdf.txtTeseACBMM.pdf.txtExtracted texttext/plain484081https://repositorio.ufscar.br/bitstream/ufscar/7699/3/TeseACBMM.pdf.txt595f71d565f6f9faf52fb77c1c5bc3d8MD53THUMBNAILTeseACBMM.pdf.jpgTeseACBMM.pdf.jpgIM Thumbnailimage/jpeg10662https://repositorio.ufscar.br/bitstream/ufscar/7699/4/TeseACBMM.pdf.jpg7e3769f4e6eaced6c800f19e2d1134eaMD54ufscar/76992023-09-18 18:31:39.981oai:repositorio.ufscar.br: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Repositório InstitucionalPUBhttps://repositorio.ufscar.br/oai/requestopendoar:43222023-09-18T18:31:39Repositório Institucional da UFSCAR - Universidade Federal de São Carlos (UFSCAR)false |
dc.title.por.fl_str_mv |
Eficácia do [10]-gingerol contra metástases de câncer de mama : estudos in vitro e in vivo em camundongos |
title |
Eficácia do [10]-gingerol contra metástases de câncer de mama : estudos in vitro e in vivo em camundongos |
spellingShingle |
Eficácia do [10]-gingerol contra metástases de câncer de mama : estudos in vitro e in vivo em camundongos Martin, Ana Carolina Baptista Moreno Câncer de mama Gingerol Metástase Cérebro Resveratrol Metastasis Natural Product [10]-gingerol Brain CIENCIAS BIOLOGICAS::GENETICA CIENCIAS DA SAUDE |
title_short |
Eficácia do [10]-gingerol contra metástases de câncer de mama : estudos in vitro e in vivo em camundongos |
title_full |
Eficácia do [10]-gingerol contra metástases de câncer de mama : estudos in vitro e in vivo em camundongos |
title_fullStr |
Eficácia do [10]-gingerol contra metástases de câncer de mama : estudos in vitro e in vivo em camundongos |
title_full_unstemmed |
Eficácia do [10]-gingerol contra metástases de câncer de mama : estudos in vitro e in vivo em camundongos |
title_sort |
Eficácia do [10]-gingerol contra metástases de câncer de mama : estudos in vitro e in vivo em camundongos |
author |
Martin, Ana Carolina Baptista Moreno |
author_facet |
Martin, Ana Carolina Baptista Moreno |
author_role |
author |
dc.contributor.authorlattes.por.fl_str_mv |
http://lattes.cnpq.br/0612591885565016 |
dc.contributor.author.fl_str_mv |
Martin, Ana Carolina Baptista Moreno |
dc.contributor.advisor1.fl_str_mv |
Araújo, Heloísa Sobreiro Selistre de |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/4065824911933203 |
dc.contributor.authorID.fl_str_mv |
ff87b9d8-6283-489e-98e2-a92223d62784 |
contributor_str_mv |
Araújo, Heloísa Sobreiro Selistre de |
dc.subject.por.fl_str_mv |
Câncer de mama Gingerol Metástase Cérebro Resveratrol |
topic |
Câncer de mama Gingerol Metástase Cérebro Resveratrol Metastasis Natural Product [10]-gingerol Brain CIENCIAS BIOLOGICAS::GENETICA CIENCIAS DA SAUDE |
dc.subject.eng.fl_str_mv |
Metastasis Natural Product [10]-gingerol Brain |
dc.subject.cnpq.fl_str_mv |
CIENCIAS BIOLOGICAS::GENETICA CIENCIAS DA SAUDE |
description |
Breast cancer is the leading cause of death in Brazil and worldwide, between the types of cancer, triple negative TNBC (Triple Negative Breast Cancer), which do not express hormone receptors, represents 20% of the cases and presents relapses within 3 years. However, the major cause of death in cancer is due the formation of metastasis. The TNBC has a greater propensity to form lung and brain metastasis. Furthermore, currently few treatments are available. Search for new target treatments, with fewer side effects is very important to treat this disease. Natural products are rich sources of molecules with antitumoral activity; among them are the gingerols, from ginger and resveratrol, from grapes. Nevertheless, not much is known about antitumor activity of [10]-gingerol (10G). Therefore, the aim of this work was to investigate the potential use of 10G as an antimetastatic molecule in in vitro and in vivo experiments. In this work, 10G had antiproliferative activity on several breast cancer cell lines (4T1BM2, 4T1BM2 shRNAβ3, 4T1Br4, MDA-MB-231, MDA-MB-231 BrM) and on a normal cell line, bEnd.3. The natural compounds affected tumor cell morphology and RSVT was able to inhibit cell migration and adhesion through vitronectin. 10G induced apoptosis via the extrinsic pathway through the increase of caspase-9, -3 and -7 expression and decrease of Bcl-2 expression, induced cell cycle arrest in G1 and subG0 phase. In in vivo models, 10G inhibited primary tumor growth and lung metastasis, as well as bone and brain metastasis. Therefore, this study was able to provide new data as 10G can be acting in tumor cells and its possible clinical application. |
publishDate |
2015 |
dc.date.issued.fl_str_mv |
2015-03-20 |
dc.date.accessioned.fl_str_mv |
2016-10-05T13:48:36Z |
dc.date.available.fl_str_mv |
2016-10-05T13:48:36Z |
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 |
MARTIN, Ana Carolina Baptista Moreno. Eficácia do [10]-gingerol contra metástases de câncer de mama : estudos in vitro e in vivo em camundongos. 2015. Tese (Doutorado em Genética Evolutiva e Biologia Molecular) – Universidade Federal de São Carlos, São Carlos, 2015. Disponível em: https://repositorio.ufscar.br/handle/ufscar/7699. |
dc.identifier.uri.fl_str_mv |
https://repositorio.ufscar.br/handle/ufscar/7699 |
identifier_str_mv |
MARTIN, Ana Carolina Baptista Moreno. Eficácia do [10]-gingerol contra metástases de câncer de mama : estudos in vitro e in vivo em camundongos. 2015. Tese (Doutorado em Genética Evolutiva e Biologia Molecular) – Universidade Federal de São Carlos, São Carlos, 2015. Disponível em: https://repositorio.ufscar.br/handle/ufscar/7699. |
url |
https://repositorio.ufscar.br/handle/ufscar/7699 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.confidence.fl_str_mv |
600 600 |
dc.relation.authority.fl_str_mv |
b61211db-d955-45b7-886e-a0cefb89980f |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal de São Carlos Câmpus São Carlos |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Genética Evolutiva e Biologia Molecular - PPGGEv |
dc.publisher.initials.fl_str_mv |
UFSCar |
publisher.none.fl_str_mv |
Universidade Federal de São Carlos Câmpus São Carlos |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UFSCAR instname:Universidade Federal de São Carlos (UFSCAR) instacron:UFSCAR |
instname_str |
Universidade Federal de São Carlos (UFSCAR) |
instacron_str |
UFSCAR |
institution |
UFSCAR |
reponame_str |
Repositório Institucional da UFSCAR |
collection |
Repositório Institucional da UFSCAR |
bitstream.url.fl_str_mv |
https://repositorio.ufscar.br/bitstream/ufscar/7699/1/TeseACBMM.pdf https://repositorio.ufscar.br/bitstream/ufscar/7699/2/license.txt https://repositorio.ufscar.br/bitstream/ufscar/7699/3/TeseACBMM.pdf.txt https://repositorio.ufscar.br/bitstream/ufscar/7699/4/TeseACBMM.pdf.jpg |
bitstream.checksum.fl_str_mv |
097b90957f143d8d696733602a92d242 ae0398b6f8b235e40ad82cba6c50031d 595f71d565f6f9faf52fb77c1c5bc3d8 7e3769f4e6eaced6c800f19e2d1134ea |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 MD5 |
repository.name.fl_str_mv |
Repositório Institucional da UFSCAR - Universidade Federal de São Carlos (UFSCAR) |
repository.mail.fl_str_mv |
|
_version_ |
1802136311602085888 |