The prohibitin-binding compound fluorizoline induces apoptosis in chronic lymphocytic leukemia cells through the upregulation of NOXA and synergizes with ibrutinib, 5-aminoimidazole-4-carboxamide riboside or venetoclax

Fluorizoline is a new synthetic molecule that induces apoptosis by selectively targeting prohibitins. In the study herein, the pro-apoptotic effect of fluorizoline was assessed in 34 primary samples from patients with chronic lymphocytic leukemia. Fluorizoline induced apoptosis in chronic lymphocyti...

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Detalles Bibliográficos
Autores: Cosialls Castel, Ana Mª, Pomares, Helena, Iglesias i Serret, Daniel, Saura-Esteller, José, Núñez-Vázquez, Sonia, González Gironés, Diana M., Banda, Esmeralda de la, Preciado Gallego, Sara, Albericio Palomera, Fernando, Lavilla Grífols, Rodolfo, Pons i Irazazábal, Gabriel, González Barca, Eva, Gil i Santano, Joan
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/121196
Acceso en línea:https://hdl.handle.net/2445/121196
Access Level:acceso abierto
Palabra clave:Apoptosi
Leucèmia limfocítica crònica
Malalties cròniques
Càncer
Apoptosis
Chronic lymphocytic leukemia
Chronic diseases
Cancer
Descripción
Sumario:Fluorizoline is a new synthetic molecule that induces apoptosis by selectively targeting prohibitins. In the study herein, the pro-apoptotic effect of fluorizoline was assessed in 34 primary samples from patients with chronic lymphocytic leukemia. Fluorizoline induced apoptosis in chronic lymphocytic leukemia cells at concentrations in the low micromolar range. All primary samples were sensitive to fluorizoline irrespective of patients' clinical or genetic features, whereas normal T lymphocytes were less sensitive. Fluorizoline increased the protein levels of the pro-apoptotic B-cell lymphoma 2 family member NOXA in chronic lymphocytic leukemia cells. Furthermore, fluorizoline synergized with ibrutinib, 5-aminoimidazole-4-carboxamide riboside or venetoclax to induce apoptosis. These results suggest that targeting prohibitins could be a new therapeutic strategy for chronic lymphocytic leukemia.

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