Inhibition of InsP3R with Xestospongin B Reduces Mitochondrial Respiration and Induces Selective Cell Death in T Cell Acute Lymphoblastic Leukemia Cells
| Autor: | Daniela Sauma, Alenka Lovy, Galdo Bustos, Ulises Ahumada-Castro, César Cárdenas, Jordi Molgó, Pablo Cruz |
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| Přispěvatelé: | Universidad Mayor [Santiago de Chile], Service d'Ingénierie Moléculaire pour la Santé (ex SIMOPRO) (SIMoS), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Universidad de Chile = University of Chile [Santiago] (UCHILE), University of California [Santa Barbara] (UC Santa Barbara), University of California (UC), This research was funded by FONDECYT #1200255, 1180385, CONICYT/FONDAP # 15150012 and CONICYT Doctoral Fellowship Program funds PC (#21180306) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
MESH: Cell Death
0301 basic medicine Mitochondrion Precursor T-Cell Lymphoblastic Leukemia-Lymphoma bioenergetics Jurkat cells lcsh:Chemistry chemistry.chemical_compound MESH: Macrocyclic Compounds 0302 clinical medicine Inositol 1 4 5-Trisphosphate Receptors Inositol Receptor Oxazoles lcsh:QH301-705.5 Spectroscopy Cell Death MESH: Oxazoles [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology General Medicine Computer Science Applications Mitochondria MESH: Precursor T-Cell Lymphoblastic Leukemia-Lymphoma MESH: Leukocytes Mononuclear medicine.anatomical_structure 030220 oncology & carcinogenesis T-ALL Programmed cell death MESH: Cell Line Tumor Macrocyclic Compounds MESH: Mitochondria T cell Cell Respiration [SDV.CAN]Life Sciences [q-bio]/Cancer Catalysis Article Inorganic Chemistry 03 medical and health sciences MESH: Inositol 1 4 5-Trisphosphate Receptors Cell Line Tumor medicine Humans cancer Physical and Theoretical Chemistry Molecular Biology MESH: Humans calcium Endoplasmic reticulum Organic Chemistry 030104 developmental biology chemistry lcsh:Biology (General) lcsh:QD1-999 Cell culture MESH: Biomarkers [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology Cancer research Leukocytes Mononuclear MESH: Cell Respiration metabolism Biomarkers |
| Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 651, p 651 (2021) International Journal of Molecular Sciences International Journal of Molecular Sciences, 2021, 22 (2), pp.651. ⟨10.3390/ijms22020651⟩ Volume 22 Issue 2 |
| ISSN: | 1661-6596 1422-0067 |
| DOI: | 10.3390/ijms22020651⟩ |
| Popis: | International audience; T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy whose chemoresistance and relapse persist as a problem despite significant advances in its chemotherapeutic treatments. Mitochondrial metabolism has emerged as an interesting therapeutic target given its essential role in maintaining bioenergetic and metabolic homeostasis. T-ALL cells are characterized by high levels of mitochondrial respiration, making them suitable for this type of intervention. Mitochondrial function is sustained by a constitutive transfer of calcium from the endoplasmic reticulum to mitochondria through the inositol 1,4,5-trisphosphate receptor (InsP3R), making T-ALL cells vulnerable to its inhibition. Here, we determine the bioenergetic profile of the T-ALL cell lines CCRF-CEM and Jurkat and evaluate their sensitivity to InsP3R inhibition with the specific inhibitor, Xestospongin B (XeB). Our results show that T-ALL cell lines exhibit higher mitochondrial respiration than non-malignant cells, which is blunted by the inhibition of the InsP3R. Prolonged treatment with XeB causes T-ALL cell death without affecting the normal counterpart. Moreover, the combination of XeB and glucocorticoids significantly enhanced cell death in the CCRF-CEM cells. The inhibition of InsP3R with XeB rises as a potential therapeutic alternative for the treatment of T-ALL. |
| Databáze: | OpenAIRE |
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