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oai:recercat.cat:2445/967662025-12-05T09:22:59Zcom_2072_1057col_2072_478799col_2072_478816col_2072_478916col_2072_478917col_2072_478933

urn:hdl:2445/96766 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 Càncer Apoptosi Mitocondris Cancer Apoptosis Mitochondria 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. 2016-03-30T15:13:02Z 2016-03-30T15:13:02Z 2015-10-19 2016-03-30T15:13:07Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 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/EU//MITOSCAFFOLD cc-by (c) Moncunill-Massaguer,Cristina et al., 2015 http://creativecommons.org/licenses/by/3.0/es info:eu-repo/semantics/openAccess Impact Journals Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)