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The BCL-2 family members NOXA and BIM mediate fluorizoline-induced apoptosis in multiple myeloma cells

descriptionPublicationkeyboard_double_arrow_right Article 01 Oct 2020 English Publisher:Elsevier BVJournal:Biochemical Pharmacology, volume 180, page 114,198 (issn: 0006-2952,

Authors: Daniel Iglesias-Serret; Ana M. Cosialls; Sonia Núñez-Vázquez; José Saura-Esteller; Sandra Sanchez-Esteban; Eva González-Barca; Gabriel Pons; +6 Authors

doi: 10.1016/j.bcp.2020.114198

pmid: 32798467

The BCL-2 family members NOXA and BIM mediate fluorizoline-induced apoptosis in multiple myeloma cells

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Abstract

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.

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Keywords

Adult, Aged, 80 and over, Male, Bcl-2-Like Protein 11, Dose-Response Relationship, Drug, Antineoplastic Agents, Apoptosis, Middle Aged, Repressor Proteins, HEK293 Cells, Proto-Oncogene Proteins c-bcl-2, Cell Line, Tumor, Prohibitins, Humans, Female, Multiple Myeloma, Cells, Cultured, Aged, Protein Binding

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