Molecular mechanisms of apoptosis induction by AICAR and the new prohibitin-binding compound fluorizoline

[eng] The pro-apoptotic effects of two new drugs have been studied for the development of new strategies for cancer treatment. On the one hand, we proved that AICAR induces apoptosis in an AMPK- and p53-independent manner in mouse embryonic fibroblasts. The analysis of the BCL-2 family members allow...

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Detalles Bibliográficos
Autor: Moncunill Massaguer, Cristina
Tipo de recurso: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2015
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/102861
Acceso en línea:https://hdl.handle.net/2445/102861
http://hdl.handle.net/10803/396235
Access Level:acceso abierto
Palabra clave:Càncer
Apoptosi
Cancer
Apoptosis
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spelling Molecular mechanisms of apoptosis induction by AICAR and the new prohibitin-binding compound fluorizolineMoncunill Massaguer, CristinaCàncerApoptosiCancerApoptosis[eng] The pro-apoptotic effects of two new drugs have been studied for the development of new strategies for cancer treatment. On the one hand, we proved that AICAR induces apoptosis in an AMPK- and p53-independent manner in mouse embryonic fibroblasts. The analysis of the BCL-2 family members allowed the identification of the BH3-only proteins BIM and NOXA as required for apoptosis induction by AICAR. In addition, we characterized the mechanism of action of fluorizoline (compound 1a), a new drug that specifically binds to prohibitin 1 and 2. The presence of prohibitins was proved to be essential for the pro-apoptotic effects of fluorizoline. Prohibitins mediate the increases in BIM and NOXA, two proteins that play a key role in the onset of apoptosis by fluorizoline.[cat] Es van estudiar els efectes pro-apoptòtics de dos fàrmacs pel possible desenvolupament de nous tractaments contra el càncer. D’una banda, es demostra que AICAR indueix apoptosi de manera independent d’AMPK i de p53 en fibroblasts embrionaris de ratolí. L’estudi dels membres de la família de BCL-2 va permetre identificar les proteïnes BH3-only BIM i NOXA com a necessàries per a la inducció d’apoptosi per AICAR. Per altra banda, es va caracteritzar el mecanisme d’acció de la fluorizolina (compost 1a), un nou fàrmac que s’uneix a la prohibitina 1 i 2. Vam demostrar que la presència de les prohibitines és necessària pels efectes pro-apoptòtics de la fluorizolina. Les prohibitines medien els augments en l’expressió de BIM i NOXA, dues proteïnes claus per a la inducció d’apoptosi per fluorizolina.Universitat de BarcelonaGil i Santano, JoanIglesias i Serret, DanielUniversitat de Barcelona. Departament de Ciències Fisiològiques II2015info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/102861http://hdl.handle.net/10803/396235Tesis Doctorals - Departament - Ciències Fisiològiques IIreponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaIngléscc-by-nc-sa, (c) Moncunill, 2015http://creativecommons.org/licenses/by-nc-sa/3.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1028612026-05-27T06:46:51Z
dc.title.none.fl_str_mv Molecular mechanisms of apoptosis induction by AICAR and the new prohibitin-binding compound fluorizoline
title Molecular mechanisms of apoptosis induction by AICAR and the new prohibitin-binding compound fluorizoline
spellingShingle Molecular mechanisms of apoptosis induction by AICAR and the new prohibitin-binding compound fluorizoline
Moncunill Massaguer, Cristina
Càncer
Apoptosi
Cancer
Apoptosis
title_short Molecular mechanisms of apoptosis induction by AICAR and the new prohibitin-binding compound fluorizoline
title_full Molecular mechanisms of apoptosis induction by AICAR and the new prohibitin-binding compound fluorizoline
title_fullStr Molecular mechanisms of apoptosis induction by AICAR and the new prohibitin-binding compound fluorizoline
title_full_unstemmed Molecular mechanisms of apoptosis induction by AICAR and the new prohibitin-binding compound fluorizoline
title_sort Molecular mechanisms of apoptosis induction by AICAR and the new prohibitin-binding compound fluorizoline
dc.creator.none.fl_str_mv Moncunill Massaguer, Cristina
author Moncunill Massaguer, Cristina
author_facet Moncunill Massaguer, Cristina
author_role author
dc.contributor.none.fl_str_mv Gil i Santano, Joan
Iglesias i Serret, Daniel
Universitat de Barcelona. Departament de Ciències Fisiològiques II
dc.subject.none.fl_str_mv Càncer
Apoptosi
Cancer
Apoptosis
topic Càncer
Apoptosi
Cancer
Apoptosis
description [eng] The pro-apoptotic effects of two new drugs have been studied for the development of new strategies for cancer treatment. On the one hand, we proved that AICAR induces apoptosis in an AMPK- and p53-independent manner in mouse embryonic fibroblasts. The analysis of the BCL-2 family members allowed the identification of the BH3-only proteins BIM and NOXA as required for apoptosis induction by AICAR. In addition, we characterized the mechanism of action of fluorizoline (compound 1a), a new drug that specifically binds to prohibitin 1 and 2. The presence of prohibitins was proved to be essential for the pro-apoptotic effects of fluorizoline. Prohibitins mediate the increases in BIM and NOXA, two proteins that play a key role in the onset of apoptosis by fluorizoline.
publishDate 2015
dc.date.none.fl_str_mv 2015
dc.type.none.fl_str_mv info:eu-repo/semantics/doctoralThesis
info:eu-repo/semantics/publishedVersion
format doctoralThesis
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/102861
http://hdl.handle.net/10803/396235
url https://hdl.handle.net/2445/102861
http://hdl.handle.net/10803/396235
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv cc-by-nc-sa, (c) Moncunill, 2015
http://creativecommons.org/licenses/by-nc-sa/3.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by-nc-sa, (c) Moncunill, 2015
http://creativecommons.org/licenses/by-nc-sa/3.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universitat de Barcelona
publisher.none.fl_str_mv Universitat de Barcelona
dc.source.none.fl_str_mv Tesis Doctorals - Departament - Ciències Fisiològiques II
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.300719

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