Targeting prohibitins induces apoptosis in acute myeloid leukemia cells
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Helena Pomares1,2, Claudia M. Palmeri1, Daniel Iglesias-Serret1, Cristina Moncunill-Massaguer1, José Saura-Esteller1, Sonia Núñez-Vázquez1, Enric Gamundi2, Montserrat Arnan2, Sara Preciado3, Fernando Albericio3,4,5, Rodolfo Lavilla3,6, Gabriel Pons1, Eva M. González-Barca2, Ana M. Cosialls1,*, Joan Gil1,*
1Departament de Ciències Fisiològiques, Universitat de Barcelona-Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Barcelona, Spain
2Servei d’Hematologia, Institut Català d'Oncologia-IDIBELL, Barcelona, Spain
3CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine, Barcelona Science Park, Barcelona, Spain
4Department of Organic Chemistry, University of Barcelona, Barcelona, Spain
5School of Chemistry and Physics, University of KwaZulu-Natal, Durban, South Africa
6Laboratory of Organic Chemistry, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain
*These authors share senior co-authorship
Joan Gil, email: email@example.com
Keywords: acute myeloid leukemia, apoptosis, prohibitins, BCL-2 family members, cancer
Received: February 10, 2016 Accepted: August 09, 2016 Published: August 17, 2016
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.
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