The BCL-2 family members NOXA and BIM mediate fluorizoline-induced apoptosis in multiple myeloma cells.
Adult
Aged
Aged, 80 and over
Antineoplastic Agents
/ administration & dosage
Apoptosis
/ drug effects
Bcl-2-Like Protein 11
/ metabolism
Cell Line, Tumor
Cells, Cultured
Dose-Response Relationship, Drug
Female
HEK293 Cells
Humans
Male
Middle Aged
Multiple Myeloma
/ drug therapy
Prohibitins
Protein Binding
/ physiology
Proto-Oncogene Proteins c-bcl-2
/ metabolism
Repressor Proteins
/ antagonists & inhibitors
Apoptosis
BIM
Cancer therapy
Multiple myeloma
NOXA
Prohibitin
Journal
Biochemical pharmacology
ISSN: 1873-2968
Titre abrégé: Biochem Pharmacol
Pays: England
ID NLM: 0101032
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
14
04
2020
revised:
10
08
2020
accepted:
11
08
2020
pubmed:
18
8
2020
medline:
1
1
2021
entrez:
18
8
2020
Statut:
ppublish
Résumé
Fluorizoline is a new synthetic molecule that induces apoptosis by selectively targeting prohibitins. In this study, we have assessed the pro-apoptotic effect of fluorizoline in 3 different multiple myeloma cell lines and 12 primary samples obtained from treatment-naïve multiple myeloma patients. Fluorizoline induced apoptosis in both multiple myeloma cell lines and primary samples at concentrations in the low micromolar range. All primary samples were sensitive to fluorizoline. Moreover, fluorizoline increased the mRNA and protein levels of the pro-apoptotic BCL-2 family member NOXA both in cell lines and primary samples analyzed. Finally, NOXA-depletion by CRISPR/Cas9 in cells that do not express BIM conferred resistance to fluorizoline-induced apoptosis in multiple myeloma cells. These results suggest that targeting prohibitins could be a new therapeutic strategy for myeloma multiple.
Identifiants
pubmed: 32798467
pii: S0006-2952(20)30434-2
doi: 10.1016/j.bcp.2020.114198
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
BCL2 protein, human
0
Bcl-2-Like Protein 11
0
PMAIP1 protein, human
0
Prohibitins
0
Proto-Oncogene Proteins c-bcl-2
0
Repressor Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
114198Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.