title: Targeting prohibitins induces apoptosis in acute myeloid leukemia cells.
abstract: Fluorizoline is a new synthetic molecule that induces apoptosis by selectively targeting prohibitins (PHBs). In this study, the pro-apoptotic effect of fluorizoline was assessed in two cell lines and 21 primary samples from patients with debut of acute myeloid leukemia (AML). Fluorizoline induced apoptosis in AML cells at concentrations in the low micromolar range. All primary samples were sensitive to fluorizoline irrespectively of patients' clinical or genetic features. In addition, fluorizoline inhibited the clonogenic capacity and induced differentiation of AML cells. Fluorizoline increased the mRNA and protein levels of the pro-apoptotic BCL-2 family member NOXA both in cell lines and primary samples analyzed. These results suggest that targeting PHBs could be a new therapeutic strategy for AML.
authors.affiliation: Departament de Ciències Fisiològiques, Universitat de Barcelona-Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Barcelona, Spain.|Servei d'Hematologia, Institut Català d'Oncologia-IDIBELL, Barcelona, Spain.
authors.forename: Helena
authors.initials: H
authors.lastname: Pomares
authors.affiliation: Departament de Ciències Fisiològiques, Universitat de Barcelona-Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Barcelona, Spain.
authors.forename: Claudia M
authors.initials: CM
authors.lastname: Palmeri
authors.affiliation: Departament de Ciències Fisiològiques, Universitat de Barcelona-Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Barcelona, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Iglesias-Serret
authors.affiliation: Departament de Ciències Fisiològiques, Universitat de Barcelona-Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Moncunill-Massaguer
authors.affiliation: Departament de Ciències Fisiològiques, Universitat de Barcelona-Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Barcelona, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Saura-Esteller
authors.affiliation: Departament de Ciències Fisiològiques, Universitat de Barcelona-Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Barcelona, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Núñez-Vázquez
authors.affiliation: Servei d'Hematologia, Institut Català d'Oncologia-IDIBELL, Barcelona, Spain.
authors.forename: Enric
authors.initials: E
authors.lastname: Gamundi
authors.affiliation: Servei d'Hematologia, Institut Català d'Oncologia-IDIBELL, Barcelona, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Arnan
authors.affiliation: CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine, Barcelona Science Park, Barcelona, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Preciado
authors.affiliation: CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine, Barcelona Science Park, Barcelona, Spain.|Department of Organic Chemistry, University of Barcelona, Barcelona, Spain.|School of Chemistry and Physics, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Fernando
authors.initials: F
authors.lastname: Albericio
authors.affiliation: CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine, Barcelona Science Park, Barcelona, Spain.|Laboratory of Organic Chemistry, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Lavilla
authors.affiliation: Departament de Ciències Fisiològiques, Universitat de Barcelona-Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Barcelona, Spain.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Pons
authors.affiliation: Servei d'Hematologia, Institut Català d'Oncologia-IDIBELL, Barcelona, Spain.
authors.forename: Eva M
authors.initials: EM
authors.lastname: González-Barca
authors.affiliation: Departament de Ciències Fisiològiques, Universitat de Barcelona-Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Barcelona, Spain.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Cosialls
authors.affiliation: Departament de Ciències Fisiològiques, Universitat de Barcelona-Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Gil
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D052160:Benzothiazoles / Q000737:chemistry / Q000494:pharmacology*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D058990:Molecular Targeted Therapy; D000091402:Prohibitins; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; D052160:Benzothiazoles; D000091402:Prohibitins; D019253:Proto-Oncogene Proteins c-bcl-2; D012097:Repressor Proteins; C058836:benzothiazoline
keywords: BCL-2 family members; acute myeloid leukemia; apoptosis; cancer; prohibitins