A novel prohibitin-binding compound induces the mitochondrial apoptotic pathway through NOXA and BIM upregulation

Moncunill Massaguer, Cristina; Saura-Esteller, José; Pérez-Perarnau, Alba; Palmeri, Claudia Mariela; Núñez-Vázquez, Sonia; Cosialls Castel, Ana Mª; González Gironés, Diana M.; Pomares, Helena; Korwitz, Anne; Preciado Gallego, Sara; Albericio Palomera, Fernando; Lavilla Grífols, Rodolfo; Pons i Irazazábal, Gabriel; Langer, Thomas; Iglesias i Serret, Daniel; Gil i Santano, Joan

A novel prohibitin-binding compound induces the mitochondrial apoptotic pathway through NOXA and BIM upregulation

We previously described diaryl trifluorothiazoline compound 1a (hereafter referred to as fluorizoline) as a first-in-class small molecule that induces p53-independent apoptosis in a wide range of tumor cell lines. Fluorizoline directly binds to prohibitin 1 and 2 (PHBs), two proteins involved in the...

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Autores:	Moncunill Massaguer, Cristina, Saura-Esteller, José, Pérez-Perarnau, Alba, Palmeri, Claudia Mariela, Núñez-Vázquez, Sonia, Cosialls Castel, Ana Mª, González Gironés, Diana M., Pomares, Helena, Korwitz, Anne, Preciado Gallego, Sara, Albericio Palomera, Fernando, Lavilla Grífols, Rodolfo, Pons i Irazazábal, Gabriel, Langer, Thomas, Iglesias i Serret, Daniel, Gil i Santano, Joan
Tipo de recurso:	artículo
Estado:	Versión publicada
Fecha de publicación:	2015
País:	España
Institución:	Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:	Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:	oai:recercat.cat:2445/96766
Acceso en línea:	https://hdl.handle.net/2445/96766
Access Level:	acceso abierto
Palabra clave:	Càncer Apoptosi Mitocondris Cancer Apoptosis Mitochondria

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spelling	A novel prohibitin-binding compound induces the mitochondrial apoptotic pathway through NOXA and BIM upregulationMoncunill Massaguer, CristinaSaura-Esteller, JoséPérez-Perarnau, AlbaPalmeri, Claudia MarielaNúñez-Vázquez, SoniaCosialls Castel, Ana MªGonzález Gironés, Diana M.Pomares, HelenaKorwitz, AnnePreciado Gallego, SaraAlbericio Palomera, FernandoLavilla Grífols, RodolfoPons i Irazazábal, GabrielLanger, ThomasIglesias i Serret, DanielGil i Santano, JoanCàncerApoptosiMitocondrisCancerApoptosisMitochondriaWe previously described diaryl trifluorothiazoline compound 1a (hereafter referred to as fluorizoline) as a first-in-class small molecule that induces p53-independent apoptosis in a wide range of tumor cell lines. Fluorizoline directly binds to prohibitin 1 and 2 (PHBs), two proteins involved in the regulation of several cellular processes, including apoptosis. Here we demonstrate that fluorizoline-induced apoptosis is mediated by PHBs, as cells depleted of these proteins are highly resistant to fluorizoline treatment. In addition, BAX and BAK are necessary for fluorizoline-induced cytotoxic effects, thereby proving that apoptosis occurs through the intrinsic pathway. Expression analysis revealed that fluorizoline induced the upregulation of Noxa and Bim mRNA levels, which was not observed in PHB-depleted MEFs. Finally, Noxa-/-/Bim-/- MEFs and NOXA-downregulated HeLa cells were resistant to fluorizoline-induced apoptosis. All together, these findings show that fluorizoline requires PHBs to execute the mitochondrial apoptotic pathway.Impact Journals2016201620152016info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion16 p.application/pdfhttps://hdl.handle.net/2445/96766Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: http://dx.doi.org/10.18632/oncotarget.6154Oncotarget, 2015, vol. 6, num. 39, p. 41750-41765http://dx.doi.org/10.18632/oncotarget.6154info:eu-repo/grantAgreement/EC/FP7/233078cc-by (c) Moncunill-Massaguer,Cristina et al., 2015http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/967662026-05-29T05:05:01Z
dc.title.none.fl_str_mv	A novel prohibitin-binding compound induces the mitochondrial apoptotic pathway through NOXA and BIM upregulation
title	A novel prohibitin-binding compound induces the mitochondrial apoptotic pathway through NOXA and BIM upregulation
spellingShingle	A novel prohibitin-binding compound induces the mitochondrial apoptotic pathway through NOXA and BIM upregulation Moncunill Massaguer, Cristina Càncer Apoptosi Mitocondris Cancer Apoptosis Mitochondria
title_short	A novel prohibitin-binding compound induces the mitochondrial apoptotic pathway through NOXA and BIM upregulation
title_full	A novel prohibitin-binding compound induces the mitochondrial apoptotic pathway through NOXA and BIM upregulation
title_fullStr	A novel prohibitin-binding compound induces the mitochondrial apoptotic pathway through NOXA and BIM upregulation
title_full_unstemmed	A novel prohibitin-binding compound induces the mitochondrial apoptotic pathway through NOXA and BIM upregulation
title_sort	A novel prohibitin-binding compound induces the mitochondrial apoptotic pathway through NOXA and BIM upregulation
dc.creator.none.fl_str_mv	Moncunill Massaguer, Cristina Saura-Esteller, José Pérez-Perarnau, Alba Palmeri, Claudia Mariela Núñez-Vázquez, Sonia Cosialls Castel, Ana Mª González Gironés, Diana M. Pomares, Helena Korwitz, Anne Preciado Gallego, Sara Albericio Palomera, Fernando Lavilla Grífols, Rodolfo Pons i Irazazábal, Gabriel Langer, Thomas Iglesias i Serret, Daniel Gil i Santano, Joan
author	Moncunill Massaguer, Cristina
author_facet	Moncunill Massaguer, Cristina Saura-Esteller, José Pérez-Perarnau, Alba Palmeri, Claudia Mariela Núñez-Vázquez, Sonia Cosialls Castel, Ana Mª González Gironés, Diana M. Pomares, Helena Korwitz, Anne Preciado Gallego, Sara Albericio Palomera, Fernando Lavilla Grífols, Rodolfo Pons i Irazazábal, Gabriel Langer, Thomas Iglesias i Serret, Daniel Gil i Santano, Joan
author_role	author
author2	Saura-Esteller, José Pérez-Perarnau, Alba Palmeri, Claudia Mariela Núñez-Vázquez, Sonia Cosialls Castel, Ana Mª González Gironés, Diana M. Pomares, Helena Korwitz, Anne Preciado Gallego, Sara Albericio Palomera, Fernando Lavilla Grífols, Rodolfo Pons i Irazazábal, Gabriel Langer, Thomas Iglesias i Serret, Daniel Gil i Santano, Joan
author2_role	author author author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	Càncer Apoptosi Mitocondris Cancer Apoptosis Mitochondria
topic	Càncer Apoptosi Mitocondris Cancer Apoptosis Mitochondria
description	We previously described diaryl trifluorothiazoline compound 1a (hereafter referred to as fluorizoline) as a first-in-class small molecule that induces p53-independent apoptosis in a wide range of tumor cell lines. Fluorizoline directly binds to prohibitin 1 and 2 (PHBs), two proteins involved in the regulation of several cellular processes, including apoptosis. Here we demonstrate that fluorizoline-induced apoptosis is mediated by PHBs, as cells depleted of these proteins are highly resistant to fluorizoline treatment. In addition, BAX and BAK are necessary for fluorizoline-induced cytotoxic effects, thereby proving that apoptosis occurs through the intrinsic pathway. Expression analysis revealed that fluorizoline induced the upregulation of Noxa and Bim mRNA levels, which was not observed in PHB-depleted MEFs. Finally, Noxa-/-/Bim-/- MEFs and NOXA-downregulated HeLa cells were resistant to fluorizoline-induced apoptosis. All together, these findings show that fluorizoline requires PHBs to execute the mitochondrial apoptotic pathway.
publishDate	2015
dc.date.none.fl_str_mv	2015 2016 2016 2016
dc.type.none.fl_str_mv	info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion
format	article
status_str	publishedVersion
dc.identifier.none.fl_str_mv	https://hdl.handle.net/2445/96766
url	https://hdl.handle.net/2445/96766
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.relation.none.fl_str_mv	Reproducció del document publicat a: http://dx.doi.org/10.18632/oncotarget.6154 Oncotarget, 2015, vol. 6, num. 39, p. 41750-41765 http://dx.doi.org/10.18632/oncotarget.6154 info:eu-repo/grantAgreement/EC/FP7/233078
dc.rights.none.fl_str_mv	cc-by (c) Moncunill-Massaguer,Cristina et al., 2015 http://creativecommons.org/licenses/by/3.0/es info:eu-repo/semantics/openAccess
rights_invalid_str_mv	cc-by (c) Moncunill-Massaguer,Cristina et al., 2015 http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	16 p. application/pdf
dc.publisher.none.fl_str_mv	Impact Journals
publisher.none.fl_str_mv	Impact Journals
dc.source.none.fl_str_mv	Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica) reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str	Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str	Recercat. Dipósit de la Recerca de Catalunya
collection	Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score	15,811543

A novel prohibitin-binding compound induces the mitochondrial apoptotic pathway through NOXA and BIM upregulation

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