دورية أكاديمية
Inhibition of InsP3R with Xestospongin B reduces mitochondrial respiration and induces selective cell death in T cell acute lymphoblastic leukemia cells
| العنوان: | Inhibition of InsP3R with Xestospongin B reduces mitochondrial respiration and induces selective cell death in T cell acute lymphoblastic leukemia cells |
|---|---|
| المؤلفون: | Cruz, Pablo, Ahumada-Castro, Ulises, Bustos, Galdo, Molgo, Jordi, Sauma, Daniela, Lovy, Alenka, Cárdenas, César |
| المساهمون: | 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-Institut des Sciences du Vivant Frédéric JOLIOT (JOLIOT), 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-Institut des Sciences du Vivant Frédéric JOLIOT (JOLIOT), 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) |
| المصدر: | ISSN: 1661-6596. |
| بيانات النشر: | HAL CCSD MDPI |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | T-ALL, bioenergetics, calcium, cancer, metabolism, MESH: Biomarkers, MESH: Cell Death, MESH: Mitochondria, MESH: Oxazoles, MESH: Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, MESH: Cell Line, Tumor, MESH: Cell Respiration, MESH: Humans, MESH: Inositol 1,4,5-Trisphosphate Receptors, MESH: Leukocytes, Mononuclear, MESH: Macrocyclic Compounds, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/33440859; hal-03630856; https://hal.science/hal-03630856Test; https://hal.science/hal-03630856/documentTest; https://hal.science/hal-03630856/file/cruZ1.pdfTest; PUBMED: 33440859; PUBMEDCENTRAL: PMC7827595 |
| DOI: | 10.3390/ijms22020651 |
| الإتاحة: | https://doi.org/10.3390/ijms22020651Test https://hal.science/hal-03630856Test https://hal.science/hal-03630856/documentTest https://hal.science/hal-03630856/file/cruZ1.pdfTest |
| حقوق: | http://creativecommons.org/licenses/byTest/ ; info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.48DCF2D1 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3390/ijms22020651 |
|---|