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| Main Authors: | , , , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
| Published: |
Free radical biology & medicine
2025
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| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/40222425/ |
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Table of Contents:
- 3-Bromopyruvate boosts the effect of chemotherapy in acute myeloid leukemia by a pro-oxidant mechanism. Pereira-Vieira, Joana Granja, Sara Celeiro, Sónia Pires Barbosa-Matos, Catarina Preto, Ana Queirós, Odília Ko, Young Hee Casal, Margarida Baltazar, Fátima Humans Pyruvates Leukemia, Myeloid, Acute Reactive Oxygen Species Cell Line, Tumor Daunorubicin Mitochondria Cytarabine Antineoplastic Agents Antioxidants Drug Synergism Antineoplastic Combined Chemotherapy Protocols Cell Proliferation Acute myeloid leukemia (AML) comprises a diverse group of blood cancers with varying genetic, phenotypic, and clinical traits, making development of targeted therapy challenging. Metabolic reprogramming in AML has been described as relevant for chemotherapy effectiveness. 3-Bromopyruvate (3-BP) is an anticancer agent that undermines energy metabolism of cancer cells. However, the effect of 3-BP in hematologic malignancies, such as AML, needs further investigation. Thus, we aimed to explore 3-BP as a chemo-sensitizing agent in AML. Different approaches of combining 3-BP with classical chemotherapy (daunorubicin and cytarabin) were tested in diverse AML cell lines. Cell sensitivity to the different drug combinations was analyzed by Trypan blue staining. The effect of pre-treatment with a non-toxic concentration of 3-BP was assessed on the AML cell metabolic profile (Western blot and immunofluorescence), mitochondrial activity (cytometry flow), and antioxidant capacity (colorimetric detection kit). KG-1 and MOLM13 cells showed increased sensitivity to chemotherapy (decreased EC values) after exposure to a non-toxic concentration (5 μM) of 3-BP. In both cell lines, 5 μM 3-BP decreased glucose consumption without changing extracellular lactate levels. 5 μM 3-BP treatment increased reactive oxygen species levels and decreased cell antioxidant capacity by depleting reduced glutathione levels in both KG-1 and MOLM13 cells. Our results demonstrate that non-toxic concentrations of 3-BP enhance the effect of classical chemotherapy in AML cells through a pro-oxidant mechanism. These data unveiled a new approach for AML treatment, using 3-BP or other pro-oxidant agents as co-adjuvants of chemotherapy, subsiding chemotherapy-induced side effects.