Cargando…
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...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ferrata Storti Foundation
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5685241/ https://www.ncbi.nlm.nih.gov/pubmed/28619845 http://dx.doi.org/10.3324/haematol.2016.162958 |
_version_ | 1783278604321292288 |
---|---|
author | Cosialls, Ana M. Pomares, Helena Iglesias-Serret, Daniel Saura-Esteller, José Núñez-Vázquez, Sonia González-Gironès, Diana M. de la Banda, Esmeralda Preciado, Sara Albericio, Fernando Lavilla, Rodolfo Pons, Gabriel González-Barca, Eva M. Gil, Joan |
author_facet | Cosialls, Ana M. Pomares, Helena Iglesias-Serret, Daniel Saura-Esteller, José Núñez-Vázquez, Sonia González-Gironès, Diana M. de la Banda, Esmeralda Preciado, Sara Albericio, Fernando Lavilla, Rodolfo Pons, Gabriel González-Barca, Eva M. Gil, Joan |
author_sort | Cosialls, Ana M. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5685241 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Ferrata Storti Foundation |
record_format | MEDLINE/PubMed |
spelling | pubmed-56852412017-11-21 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 Cosialls, Ana M. Pomares, Helena Iglesias-Serret, Daniel Saura-Esteller, José Núñez-Vázquez, Sonia González-Gironès, Diana M. de la Banda, Esmeralda Preciado, Sara Albericio, Fernando Lavilla, Rodolfo Pons, Gabriel González-Barca, Eva M. Gil, Joan Haematologica Article 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. Ferrata Storti Foundation 2017-09 /pmc/articles/PMC5685241/ /pubmed/28619845 http://dx.doi.org/10.3324/haematol.2016.162958 Text en Copyright© 2017 Ferrata Storti Foundation Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or internal use. Sharing published material for non-commercial purposes is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for commercial purposes is not allowed without permission in writing from the publisher. |
spellingShingle | Article Cosialls, Ana M. Pomares, Helena Iglesias-Serret, Daniel Saura-Esteller, José Núñez-Vázquez, Sonia González-Gironès, Diana M. de la Banda, Esmeralda Preciado, Sara Albericio, Fernando Lavilla, Rodolfo Pons, Gabriel González-Barca, Eva M. Gil, Joan 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 |
title | 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 |
title_full | 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 |
title_fullStr | 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 |
title_full_unstemmed | 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 |
title_short | 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 |
title_sort | 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 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5685241/ https://www.ncbi.nlm.nih.gov/pubmed/28619845 http://dx.doi.org/10.3324/haematol.2016.162958 |
work_keys_str_mv | AT cosiallsanam theprohibitinbindingcompoundfluorizolineinducesapoptosisinchroniclymphocyticleukemiacellsthroughtheupregulationofnoxaandsynergizeswithibrutinib5aminoimidazole4carboxamideribosideorvenetoclax AT pomareshelena theprohibitinbindingcompoundfluorizolineinducesapoptosisinchroniclymphocyticleukemiacellsthroughtheupregulationofnoxaandsynergizeswithibrutinib5aminoimidazole4carboxamideribosideorvenetoclax AT iglesiasserretdaniel theprohibitinbindingcompoundfluorizolineinducesapoptosisinchroniclymphocyticleukemiacellsthroughtheupregulationofnoxaandsynergizeswithibrutinib5aminoimidazole4carboxamideribosideorvenetoclax AT sauraestellerjose theprohibitinbindingcompoundfluorizolineinducesapoptosisinchroniclymphocyticleukemiacellsthroughtheupregulationofnoxaandsynergizeswithibrutinib5aminoimidazole4carboxamideribosideorvenetoclax AT nunezvazquezsonia theprohibitinbindingcompoundfluorizolineinducesapoptosisinchroniclymphocyticleukemiacellsthroughtheupregulationofnoxaandsynergizeswithibrutinib5aminoimidazole4carboxamideribosideorvenetoclax AT gonzalezgironesdianam theprohibitinbindingcompoundfluorizolineinducesapoptosisinchroniclymphocyticleukemiacellsthroughtheupregulationofnoxaandsynergizeswithibrutinib5aminoimidazole4carboxamideribosideorvenetoclax AT delabandaesmeralda theprohibitinbindingcompoundfluorizolineinducesapoptosisinchroniclymphocyticleukemiacellsthroughtheupregulationofnoxaandsynergizeswithibrutinib5aminoimidazole4carboxamideribosideorvenetoclax AT preciadosara theprohibitinbindingcompoundfluorizolineinducesapoptosisinchroniclymphocyticleukemiacellsthroughtheupregulationofnoxaandsynergizeswithibrutinib5aminoimidazole4carboxamideribosideorvenetoclax AT albericiofernando theprohibitinbindingcompoundfluorizolineinducesapoptosisinchroniclymphocyticleukemiacellsthroughtheupregulationofnoxaandsynergizeswithibrutinib5aminoimidazole4carboxamideribosideorvenetoclax AT lavillarodolfo theprohibitinbindingcompoundfluorizolineinducesapoptosisinchroniclymphocyticleukemiacellsthroughtheupregulationofnoxaandsynergizeswithibrutinib5aminoimidazole4carboxamideribosideorvenetoclax AT ponsgabriel theprohibitinbindingcompoundfluorizolineinducesapoptosisinchroniclymphocyticleukemiacellsthroughtheupregulationofnoxaandsynergizeswithibrutinib5aminoimidazole4carboxamideribosideorvenetoclax AT gonzalezbarcaevam theprohibitinbindingcompoundfluorizolineinducesapoptosisinchroniclymphocyticleukemiacellsthroughtheupregulationofnoxaandsynergizeswithibrutinib5aminoimidazole4carboxamideribosideorvenetoclax AT giljoan theprohibitinbindingcompoundfluorizolineinducesapoptosisinchroniclymphocyticleukemiacellsthroughtheupregulationofnoxaandsynergizeswithibrutinib5aminoimidazole4carboxamideribosideorvenetoclax AT cosiallsanam prohibitinbindingcompoundfluorizolineinducesapoptosisinchroniclymphocyticleukemiacellsthroughtheupregulationofnoxaandsynergizeswithibrutinib5aminoimidazole4carboxamideribosideorvenetoclax AT pomareshelena prohibitinbindingcompoundfluorizolineinducesapoptosisinchroniclymphocyticleukemiacellsthroughtheupregulationofnoxaandsynergizeswithibrutinib5aminoimidazole4carboxamideribosideorvenetoclax AT iglesiasserretdaniel prohibitinbindingcompoundfluorizolineinducesapoptosisinchroniclymphocyticleukemiacellsthroughtheupregulationofnoxaandsynergizeswithibrutinib5aminoimidazole4carboxamideribosideorvenetoclax AT sauraestellerjose prohibitinbindingcompoundfluorizolineinducesapoptosisinchroniclymphocyticleukemiacellsthroughtheupregulationofnoxaandsynergizeswithibrutinib5aminoimidazole4carboxamideribosideorvenetoclax AT nunezvazquezsonia prohibitinbindingcompoundfluorizolineinducesapoptosisinchroniclymphocyticleukemiacellsthroughtheupregulationofnoxaandsynergizeswithibrutinib5aminoimidazole4carboxamideribosideorvenetoclax AT gonzalezgironesdianam prohibitinbindingcompoundfluorizolineinducesapoptosisinchroniclymphocyticleukemiacellsthroughtheupregulationofnoxaandsynergizeswithibrutinib5aminoimidazole4carboxamideribosideorvenetoclax AT delabandaesmeralda prohibitinbindingcompoundfluorizolineinducesapoptosisinchroniclymphocyticleukemiacellsthroughtheupregulationofnoxaandsynergizeswithibrutinib5aminoimidazole4carboxamideribosideorvenetoclax AT preciadosara prohibitinbindingcompoundfluorizolineinducesapoptosisinchroniclymphocyticleukemiacellsthroughtheupregulationofnoxaandsynergizeswithibrutinib5aminoimidazole4carboxamideribosideorvenetoclax AT albericiofernando prohibitinbindingcompoundfluorizolineinducesapoptosisinchroniclymphocyticleukemiacellsthroughtheupregulationofnoxaandsynergizeswithibrutinib5aminoimidazole4carboxamideribosideorvenetoclax AT lavillarodolfo prohibitinbindingcompoundfluorizolineinducesapoptosisinchroniclymphocyticleukemiacellsthroughtheupregulationofnoxaandsynergizeswithibrutinib5aminoimidazole4carboxamideribosideorvenetoclax AT ponsgabriel prohibitinbindingcompoundfluorizolineinducesapoptosisinchroniclymphocyticleukemiacellsthroughtheupregulationofnoxaandsynergizeswithibrutinib5aminoimidazole4carboxamideribosideorvenetoclax AT gonzalezbarcaevam prohibitinbindingcompoundfluorizolineinducesapoptosisinchroniclymphocyticleukemiacellsthroughtheupregulationofnoxaandsynergizeswithibrutinib5aminoimidazole4carboxamideribosideorvenetoclax AT giljoan prohibitinbindingcompoundfluorizolineinducesapoptosisinchroniclymphocyticleukemiacellsthroughtheupregulationofnoxaandsynergizeswithibrutinib5aminoimidazole4carboxamideribosideorvenetoclax |