Universität zu Köln

Moncunill-Massaguer, Cristina, Saura-Esteller, Jose ORCID: 0000-0001-6924-7798, Perez-Perarnau, Alba, Mariela Palmeri, Claudia, Nunez-Vazquez, Sonia, Cosialls, Ana M., Gonzalez-Girones, Diana M., Pomares, Helena, Korwitz, Anne, Preciado, Sara, Albericio, Fernando, Lavilla, Rodolfo, Pons, Gabriel, Langer, Thomas ORCID: 0000-0003-1250-1462, Iglesias-Serret, Daniel ORCID: 0000-0001-8656-1308 and Gil, Joan ORCID: 0000-0002-3686-3903 (2015). A novel prohibitin-binding compound induces the mitochondrial apoptotic pathway through NOXA and BIM upregulation. Oncotarget, 6 (39). S. 41750 - 41766. ORCHARD PARK: IMPACT JOURNALS LLC. ISSN 1949-2553

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Moncunill-Massaguer, Cristina UNSPECIFIED UNSPECIFIED UNSPECIFIED Saura-Esteller, Jose UNSPECIFIED orcid.org/0000-0001-6924-7798 UNSPECIFIED Perez-Perarnau, Alba UNSPECIFIED UNSPECIFIED UNSPECIFIED Mariela Palmeri, Claudia UNSPECIFIED UNSPECIFIED UNSPECIFIED Nunez-Vazquez, Sonia UNSPECIFIED UNSPECIFIED UNSPECIFIED Cosialls, Ana M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gonzalez-Girones, Diana M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Pomares, Helena UNSPECIFIED UNSPECIFIED UNSPECIFIED Korwitz, Anne UNSPECIFIED UNSPECIFIED UNSPECIFIED Preciado, Sara UNSPECIFIED UNSPECIFIED UNSPECIFIED Albericio, Fernando UNSPECIFIED UNSPECIFIED UNSPECIFIED Lavilla, Rodolfo UNSPECIFIED UNSPECIFIED UNSPECIFIED Pons, Gabriel UNSPECIFIED UNSPECIFIED UNSPECIFIED Langer, Thomas UNSPECIFIED orcid.org/0000-0003-1250-1462 UNSPECIFIED Iglesias-Serret, Daniel UNSPECIFIED orcid.org/0000-0001-8656-1308 UNSPECIFIED Gil, Joan UNSPECIFIED orcid.org/0000-0002-3686-3903 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-383820
DOI:	10.18632/oncotarget.6154
Journal or Publication Title:	Oncotarget
Volume:	6
Number:	39
Page Range:	S. 41750 - 41766
Date:	2015
Publisher:	IMPACT JOURNALS LLC
Place of Publication:	ORCHARD PARK
ISSN:	1949-2553
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CYTOCHROME-C RELEASE; CELL-DEATH; BCL-2 FAMILY; PROTEASE OMA1; OPA1; BAK; PROLIFERATION; ACTIVATION; PROTEINS; CRISTAE Multiple languages Oncology; Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/38382