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Inhibition of InsP3R with Xestospongin B Reduces Mitochondrial Respiration and Induces Selective Cell Death in T Cell Acute Lymphoblastic Leukemia Cells.
Cruz, Pablo; Ahumada-Castro, Ulises; Bustos, Galdo; Molgó, Jordi; Sauma, Daniela; Lovy, Alenka; Cárdenas, César.
Afiliação
  • Cruz P; Center for Integrative Biology, Faculty of Sciences, Universidad Mayor, Santiago 8580745, Chile.
  • Ahumada-Castro U; Center for Integrative Biology, Faculty of Sciences, Universidad Mayor, Santiago 8580745, Chile.
  • Bustos G; Geroscience Center for Brain Health and Metabolism, Santiago 8580745, Chile.
  • Molgó J; Center for Integrative Biology, Faculty of Sciences, Universidad Mayor, Santiago 8580745, Chile.
  • Sauma D; Geroscience Center for Brain Health and Metabolism, Santiago 8580745, Chile.
  • Lovy A; Département Médicaments et Technologies pour la Santé, Service d'Ingénierie Moléculaire pour la Santé (SIMoS), ERL CNRS n° 9004, Institut des Sciences du Vivant Frédéric Joliot, CEA, Université Paris-Saclay, bâtiment 152, Point courrier 24, F-91191 Gif sur Yvette, France.
  • Cárdenas C; Biology Department, Faculty of Science, Universidad de Chile, Santiago 8330015, Chile.
Int J Mol Sci ; 22(2)2021 Jan 11.
Article em En | MEDLINE | ID: mdl-33440859
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Oxazóis / Respiração Celular / Compostos Macrocíclicos / Receptores de Inositol 1,4,5-Trifosfato / Leucemia-Linfoma Linfoblástico de Células T Precursoras / Mitocôndrias Tipo de estudo: Etiology_studies Limite: Humans Idioma: En Revista: Int J Mol Sci Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Chile País de publicação: Suíça
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Oxazóis / Respiração Celular / Compostos Macrocíclicos / Receptores de Inositol 1,4,5-Trifosfato / Leucemia-Linfoma Linfoblástico de Células T Precursoras / Mitocôndrias Tipo de estudo: Etiology_studies Limite: Humans Idioma: En Revista: Int J Mol Sci Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Chile País de publicação: Suíça