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http://hdl.handle.net/2445/96766
Title: | A novel prohibitin-binding compound induces the mitochondrial apoptotic pathway through NOXA and BIM upregulation |
Author: | 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 |
Keywords: | Càncer Apoptosi Mitocondris Cancer Apoptosis Mitochondria |
Issue Date: | 19-Oct-2015 |
Publisher: | Impact Journals |
Abstract: | 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. |
Note: | Reproducció del document publicat a: http://dx.doi.org/10.18632/oncotarget.6154 |
It is part of: | Oncotarget, 2015, vol. 6, num. 39, p. 41750-41765 |
URI: | http://hdl.handle.net/2445/96766 |
Related resource: | http://dx.doi.org/10.18632/oncotarget.6154 |
ISSN: | 1949-2553 |
Appears in Collections: | Articles publicats en revistes (Ciències Fisiològiques) Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica) Articles publicats en revistes (Química Inorgànica i Orgànica) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) Publicacions de projectes de recerca finançats per la UE |
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