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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
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:
It is part of: Oncotarget, 2015, vol. 6, num. 39, p. 41750-41765
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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)

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