Seleção de novas moléculas e modalidades de tratamento no combate ao câncer
Ano de defesa: | 2012 |
---|---|
Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | |
Tipo de documento: | Tese |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Federal de Pelotas
|
Programa de Pós-Graduação: |
Programa de Pós-Graduação em Biotecnologia
|
Departamento: |
Biotecnologia
|
País: |
BR
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://repositorio.ufpel.edu.br/handle/ri/1209 |
Resumo: | Cancer is a leading cause of death and its rates are expected to increase 50% by 2020. Although surgical resection and additional therapies (such as chemotherapy and radiotherapy) are able to cure well-confined, primary tumors, the same does not apply during metastasis due to the systemic involvement and its resistance to conventional therapies. Therefore, the current clinical challenge is to develop new drugs and treatment modalities that will significantly impact the cure rates. In this sense, the present study aimed to evaluate the anticancer effect and study the underlying cell death mechanisms of diaryl diselenides and its substituted structures - (4-ClC6H4Se)2, (3-CF3C6H4Se)2 e (4-MeOC6H4Se)2 - on the human colon adenocarcinoma cell line (HT-29). We verified that (3-CF3C6H4Se)2 and (4-MeOC6H4Se)2 induced cytotoxicity through apoptosis mechanisms in HT-29 cells, where pro-apoptotic genes were up-regulated (Bax, caspase-9, caspase-8, apoptosis-inducing factor (AIF) and endonuclease G (EndoG), and anti-apoptotic genes were down-regulated (Bcl-2 and survivin). In a second moment we evaluated the anticancer potential of Canavalia brasiliensis (ConBr), Canavalia boliviana (ConBol) and Canavalia ensiformis (ConA) lectins in HT-29 cells, which showed an effective capacity to reduce cell viability. Once the anticancer effect was confirmed, lectins were labeled with FITC and its interaction with the tumor cells was investigated. The FITC-ConA and FITC-ConBol demonstrated the potential to bind to HT-29 cells unlike FITC-ConBr. In order to investigate a new treatment modality, the interaction between the respective lectins with HT-29 was evaluated when associated with functionalized multi-walled carbon nanotubes (f-MWCNTs). When f-MWNT was incorporated to FITC-ConBol and FITC-ConA lectins there was an increase in fluorescence intensity. |
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2014-08-20T13:32:46Z2013-10-312014-08-20T13:32:46Z2012-09-17NEDEL, Fernanda. Selection of new molecules and treatment modalities to fight cancer. 2012. 89 f. Tese (Doutorado em Biotecnologia) - Universidade Federal de Pelotas, Pelotas, 2012.http://repositorio.ufpel.edu.br/handle/ri/1209Cancer is a leading cause of death and its rates are expected to increase 50% by 2020. Although surgical resection and additional therapies (such as chemotherapy and radiotherapy) are able to cure well-confined, primary tumors, the same does not apply during metastasis due to the systemic involvement and its resistance to conventional therapies. Therefore, the current clinical challenge is to develop new drugs and treatment modalities that will significantly impact the cure rates. In this sense, the present study aimed to evaluate the anticancer effect and study the underlying cell death mechanisms of diaryl diselenides and its substituted structures - (4-ClC6H4Se)2, (3-CF3C6H4Se)2 e (4-MeOC6H4Se)2 - on the human colon adenocarcinoma cell line (HT-29). We verified that (3-CF3C6H4Se)2 and (4-MeOC6H4Se)2 induced cytotoxicity through apoptosis mechanisms in HT-29 cells, where pro-apoptotic genes were up-regulated (Bax, caspase-9, caspase-8, apoptosis-inducing factor (AIF) and endonuclease G (EndoG), and anti-apoptotic genes were down-regulated (Bcl-2 and survivin). In a second moment we evaluated the anticancer potential of Canavalia brasiliensis (ConBr), Canavalia boliviana (ConBol) and Canavalia ensiformis (ConA) lectins in HT-29 cells, which showed an effective capacity to reduce cell viability. Once the anticancer effect was confirmed, lectins were labeled with FITC and its interaction with the tumor cells was investigated. The FITC-ConA and FITC-ConBol demonstrated the potential to bind to HT-29 cells unlike FITC-ConBr. In order to investigate a new treatment modality, the interaction between the respective lectins with HT-29 was evaluated when associated with functionalized multi-walled carbon nanotubes (f-MWCNTs). When f-MWNT was incorporated to FITC-ConBol and FITC-ConA lectins there was an increase in fluorescence intensity.O câncer é uma das principais causas de morte no mundo, onde os índices devem aumentar 50% até 2020. Embora a ressecção cirúrgica e terapias adicionais (como a quimioterapias e radioterapias) sejam capazes de curar tumores primários bem delimitados, o mesmo não se aplica a metástase devido ao seu envolvimento sistêmico e a resistência a terapias convencionais. Portanto, atualmente o desfio clínico é desenvolver novas drogas e modalidades de tratamentos que irão impactar significativamente as taxas de cura do câncer. Neste sentido, o presente trabalho objetivou avaliar o efeito antineoplásico e investigar a rota de apoptose induzido pelo disseleneto de diarila e seus derivados substituídos - (4-ClC6H4Se)2, (3-CF3C6H4Se)2 e (4-MeOC6H4Se)2 - em células de adenocarcinoma de colorretal humano (HT-29). Verificamos que os compostos (3-CF3C6H4Se)2 e (4-MeOC6H4Se)2 induziram um efeito citotoxidade por meio de apoptose, onde os genes pró-apoptoticos (Bax, caspase-9, caspase-8, fator indutor de apoptose (AIF) e endonuclease G (EndoG)) foram altamente expressos e os genes anti-apoptótico (Bcl-2 e survivin) mostraram uma redução na sua expressão. Em um segundo momento avaliamos o potencial antineoplásico das lectinas Canavalia brasiliensis (ConBr), Canavalia boliviana (ConBol) e Canavalia ensiformis (ConA) em células HT-29, as quais se mostraram efetivas em reduzir a viabilidade celular. Uma vez confirmado o efeito antineoplásico, as lectinas forma marcadas com FITC e a sua interação com as células tumorais foi investigado. As lectinas FITC-ConA e FITC-ConBol demonstraram potencial de se ligar as células HT-29 ao contrário da FITC-ConBr. A fim de investigar uma nova modalidade de tratamento foi avaliada a interação entre as respectivas lectinas com as células HT-29 quando associadas à nanotubos de carbonos funcionalizados de paredes múltiplas (f-MWCNTs). Quando os f-MWCNTs foram incorporados as lectinas FITC-ConA e FITC-ConBol houve um aumentaram na intensidade de fluorescência.application/pdfporUniversidade Federal de PelotasPrograma de Pós-Graduação em BiotecnologiaUFPelBRBiotecnologiaBiotecnologiaAdenocarcinoma de colorretal humanoDisseleneto de diarila e seus derivados substituídosLectinasNanotubos de carbonoBiotechnologyHuman colon adenocarcinomaSubstituted diaryl diselenidesLectinsCarbon nanotubesCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICASeleção de novas moléculas e modalidades de tratamento no combate ao câncerSelection of new molecules and treatment modalities to fight cancerinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesishttp://lattes.cnpq.br/9529308180586356http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4779073P1Collares, Tiago VeirasTarquino, Sandra Beatriz ChavesSandra Beatriz Chaves TarquinoSeixas, Fabiana KömmlingNedel, Fernandainfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFPel - Guaiacainstname:Universidade Federal de Pelotas (UFPEL)instacron:UFPELORIGINALtese_fernanda_nedel.pdfapplication/pdf5232153http://guaiaca.ufpel.edu.br/xmlui/bitstream/123456789/1209/1/tese_fernanda_nedel.pdf94c9f4584571a1e142e44a8b165fc8ddMD51open accessTEXTtese_fernanda_nedel.pdf.txttese_fernanda_nedel.pdf.txtExtracted Texttext/plain114322http://guaiaca.ufpel.edu.br/xmlui/bitstream/123456789/1209/2/tese_fernanda_nedel.pdf.txtc88328229331e4b4611717cf407f72bcMD52open accessTHUMBNAILtese_fernanda_nedel.pdf.jpgtese_fernanda_nedel.pdf.jpgGenerated Thumbnailimage/jpeg1770http://guaiaca.ufpel.edu.br/xmlui/bitstream/123456789/1209/3/tese_fernanda_nedel.pdf.jpg929f9fddde5106cb3d95e96f02ebff46MD53open access123456789/12092019-08-23 10:44:30.736open accessoai:guaiaca.ufpel.edu.br:123456789/1209Repositório InstitucionalPUBhttp://repositorio.ufpel.edu.br/oai/requestrippel@ufpel.edu.br || repositorio@ufpel.edu.br || aline.batista@ufpel.edu.bropendoar:2019-08-23T13:44:30Repositório Institucional da UFPel - Guaiaca - Universidade Federal de Pelotas (UFPEL)false |
dc.title.por.fl_str_mv |
Seleção de novas moléculas e modalidades de tratamento no combate ao câncer |
dc.title.alternative.eng.fl_str_mv |
Selection of new molecules and treatment modalities to fight cancer |
title |
Seleção de novas moléculas e modalidades de tratamento no combate ao câncer |
spellingShingle |
Seleção de novas moléculas e modalidades de tratamento no combate ao câncer Nedel, Fernanda Biotecnologia Adenocarcinoma de colorretal humano Disseleneto de diarila e seus derivados substituídos Lectinas Nanotubos de carbono Biotechnology Human colon adenocarcinoma Substituted diaryl diselenides Lectins Carbon nanotubes CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
Seleção de novas moléculas e modalidades de tratamento no combate ao câncer |
title_full |
Seleção de novas moléculas e modalidades de tratamento no combate ao câncer |
title_fullStr |
Seleção de novas moléculas e modalidades de tratamento no combate ao câncer |
title_full_unstemmed |
Seleção de novas moléculas e modalidades de tratamento no combate ao câncer |
title_sort |
Seleção de novas moléculas e modalidades de tratamento no combate ao câncer |
author |
Nedel, Fernanda |
author_facet |
Nedel, Fernanda |
author_role |
author |
dc.contributor.authorLattes.por.fl_str_mv |
http://lattes.cnpq.br/9529308180586356 |
dc.contributor.advisorLattes.por.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4779073P1 |
dc.contributor.referees1.pt_BR.fl_str_mv |
Tarquino, Sandra Beatriz Chaves |
dc.contributor.referees1ID.por.fl_str_mv |
|
dc.contributor.referees1Lattes.por.fl_str_mv |
Sandra Beatriz Chaves Tarquino |
dc.contributor.advisor-co1.fl_str_mv |
Collares, Tiago Veiras |
dc.contributor.advisor1.fl_str_mv |
Seixas, Fabiana Kömmling |
dc.contributor.author.fl_str_mv |
Nedel, Fernanda |
contributor_str_mv |
Collares, Tiago Veiras Seixas, Fabiana Kömmling |
dc.subject.por.fl_str_mv |
Biotecnologia Adenocarcinoma de colorretal humano Disseleneto de diarila e seus derivados substituídos Lectinas Nanotubos de carbono |
topic |
Biotecnologia Adenocarcinoma de colorretal humano Disseleneto de diarila e seus derivados substituídos Lectinas Nanotubos de carbono Biotechnology Human colon adenocarcinoma Substituted diaryl diselenides Lectins Carbon nanotubes CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
dc.subject.eng.fl_str_mv |
Biotechnology Human colon adenocarcinoma Substituted diaryl diselenides Lectins Carbon nanotubes |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
Cancer is a leading cause of death and its rates are expected to increase 50% by 2020. Although surgical resection and additional therapies (such as chemotherapy and radiotherapy) are able to cure well-confined, primary tumors, the same does not apply during metastasis due to the systemic involvement and its resistance to conventional therapies. Therefore, the current clinical challenge is to develop new drugs and treatment modalities that will significantly impact the cure rates. In this sense, the present study aimed to evaluate the anticancer effect and study the underlying cell death mechanisms of diaryl diselenides and its substituted structures - (4-ClC6H4Se)2, (3-CF3C6H4Se)2 e (4-MeOC6H4Se)2 - on the human colon adenocarcinoma cell line (HT-29). We verified that (3-CF3C6H4Se)2 and (4-MeOC6H4Se)2 induced cytotoxicity through apoptosis mechanisms in HT-29 cells, where pro-apoptotic genes were up-regulated (Bax, caspase-9, caspase-8, apoptosis-inducing factor (AIF) and endonuclease G (EndoG), and anti-apoptotic genes were down-regulated (Bcl-2 and survivin). In a second moment we evaluated the anticancer potential of Canavalia brasiliensis (ConBr), Canavalia boliviana (ConBol) and Canavalia ensiformis (ConA) lectins in HT-29 cells, which showed an effective capacity to reduce cell viability. Once the anticancer effect was confirmed, lectins were labeled with FITC and its interaction with the tumor cells was investigated. The FITC-ConA and FITC-ConBol demonstrated the potential to bind to HT-29 cells unlike FITC-ConBr. In order to investigate a new treatment modality, the interaction between the respective lectins with HT-29 was evaluated when associated with functionalized multi-walled carbon nanotubes (f-MWCNTs). When f-MWNT was incorporated to FITC-ConBol and FITC-ConA lectins there was an increase in fluorescence intensity. |
publishDate |
2012 |
dc.date.issued.fl_str_mv |
2012-09-17 |
dc.date.available.fl_str_mv |
2013-10-31 2014-08-20T13:32:46Z |
dc.date.accessioned.fl_str_mv |
2014-08-20T13:32:46Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
NEDEL, Fernanda. Selection of new molecules and treatment modalities to fight cancer. 2012. 89 f. Tese (Doutorado em Biotecnologia) - Universidade Federal de Pelotas, Pelotas, 2012. |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufpel.edu.br/handle/ri/1209 |
identifier_str_mv |
NEDEL, Fernanda. Selection of new molecules and treatment modalities to fight cancer. 2012. 89 f. Tese (Doutorado em Biotecnologia) - Universidade Federal de Pelotas, Pelotas, 2012. |
url |
http://repositorio.ufpel.edu.br/handle/ri/1209 |
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por |
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Universidade Federal de Pelotas |
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Programa de Pós-Graduação em Biotecnologia |
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UFPel |
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BR |
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Biotecnologia |
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Universidade Federal de Pelotas |
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