The BCL-2 family members NOXA and BIM mediate fluorizoline-induced apoptosis in multiple myeloma cells
| Autor: | José Saura-Esteller, Helena Pomares, Ismael Sánchez-Vera, Sonia Núñez-Vázquez, Daniel Iglesias-Serret, Ana M. Cosialls, Eva González-Barca, Gabriel Pons, Claudia M. Palmeri, Joan Gil, Rodolfo Lavilla, Sandra Sanchez-Esteban, Judit Perramon-Andújar |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Adult Male Antineoplastic Agents Apoptosis Biochemistry 03 medical and health sciences 0302 clinical medicine hemic and lymphatic diseases Cell Line Tumor Prohibitins medicine CRISPR Humans Prohibitin Multiple myeloma Cells Cultured Aged Pharmacology Aged 80 and over Messenger RNA Bcl-2-Like Protein 11 Dose-Response Relationship Drug Chemistry Cas9 Bcl-2 family Middle Aged medicine.disease Repressor Proteins 030104 developmental biology HEK293 Cells Proto-Oncogene Proteins c-bcl-2 Cell culture 030220 oncology & carcinogenesis Cancer research Female Multiple Myeloma Protein Binding |
| Zdroj: | Biochemical pharmacology. 180 |
| ISSN: | 1873-2968 |
| Popis: | 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-naive 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. |
| Databáze: | OpenAIRE |
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