Diphenyleneiodonium Triggers Cell Death of Acute Myeloid Leukemia Cells by Blocking the Mitochondrial Respiratory Chain, and Synergizes with Cytarabine - Université de Tours Accéder directement au contenu
Article Dans Une Revue Cancers Année : 2022

Diphenyleneiodonium Triggers Cell Death of Acute Myeloid Leukemia Cells by Blocking the Mitochondrial Respiratory Chain, and Synergizes with Cytarabine

Résumé

Acute myeloid leukemia (AML) is characterized by the accumulation of undifferentiated blast cells in the bone marrow and blood. In most cases of AML, relapse frequently occurs due to resistance to chemotherapy. Compelling research results indicate that drug resistance in cancer cells is highly dependent on the intracellular levels of reactive oxygen species (ROS). Modulating ROS levels is therefore a valuable strategy to overcome the chemotherapy resistance of leukemic cells. In this study, we evaluated the efficiency of diphenyleneiodonium (DPI)—a well-known inhibitor of ROS production—in targeting AML cells. Results showed that although inhibiting cytoplasmic ROS production, DPI also triggered an increase in the mitochondrial ROS levels, caused by the disruption of the mitochondrial respiratory chain. We also demonstrated that DPI blocks mitochondrial oxidative phosphorylation (OxPhos) in a dose-dependent manner, and that AML cells with high OxPhos status are highly sensitive to treatment with DPI, which synergizes with the chemotherapeutic agent cytarabine (Ara-C). Thus, our results suggest that targeting mitochondrial function with DPI might be exploited to target AML cells with high OxPhos status.
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Dates et versions

hal-03799724 , version 1 (06-10-2022)

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Hassan Dakik, Maya El Dor, Jérôme Bourgeais, Farah Kouzi, Olivier Herault, et al.. Diphenyleneiodonium Triggers Cell Death of Acute Myeloid Leukemia Cells by Blocking the Mitochondrial Respiratory Chain, and Synergizes with Cytarabine. Cancers, 2022, 14 (10), pp.2485. ⟨10.3390/cancers14102485⟩. ⟨hal-03799724⟩

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