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
Descripción
Sumario:[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.