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3-Bromopyruvate boosts the effect of chemotherapy in acute myeloid leukemia by a pro-oxidant mechanism

2025-07Artigo de investigação Acesso embargado
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dc.contributor.authorVieira, Joana Pereira
dc.contributor.authorPreto, Ana
dc.contributor.authorGranja, Sara
dc.contributor.authorQueirós, Odília
dc.contributor.authorCeleiro, Sónia Pires
dc.contributor.authorKo, Young Hee
dc.contributor.authorCasal, Margarida
dc.contributor.authorMatos, Catarina Barbosa
dc.contributor.authorBaltazar, Fátima
dc.contributor.authorGranja, Sara
dc.date.accessioned2026-01-15T14:42:30Z
dc.date.available2026-01-15T14:42:30Z
dc.date.issued2025-07
dc.description.abstractAcute 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 50 values) after exposure to a non-toxic concentration (5 μ M) of 3-BP. In both cell lines, 5 glucose consumption without changing extracellular lactate levels. 5 μ μ M 3-BP decreased M 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.eng
dc.description.sponsorshipUIDB/50026/2020, UIDP/50026/2020, NORTE-01-0145-FEDER-000039, NORTE-01-0145-FEDER-000055, and UID/BIA/04050/2020
dc.identifier.citationPereira-Vieira, J., Granja, S., Celeiro, S. P., Barbosa-Matos, C., Preto, A., Queirós, O., Ko, Y. H., Casal, M., & Baltazar, F. (2025). 3-Bromopyruvate boosts the effect of chemotherapy in acute myeloid leukemia by a pro-oxidant mechanism. Free Radical Biology and Medicine, 234, 192–202. https://doi.org/10.1016/j.freeradbiomed.2025.04.017
dc.identifier.doi10.1016/j.freeradbiomed.2025.04.017
dc.identifier.eissn1873-4596
dc.identifier.issn0891-5849
dc.identifier.urihttp://hdl.handle.net/10400.22/31540
dc.language.isoeng
dc.peerreviewedyes
dc.publisherElsevier
dc.relationPPBI, ref. PPBI-POCI- 01-0145-FEDER-022122); (ref. SFRH/BD/146065/2019, 2020.05779.BD, SFRH/BD/145955/2019, and COVID/BD/153456/ 2023).
dc.relation.hasversionhttps://www.sciencedirect.com/science/article/pii/S0891584925002278?via%3Dihub
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectBlood cancer
dc.subjectCancer metabolism
dc.subjectCytarabine
dc.subjectDaunorubicin
dc.subjectOxidative stress
dc.title3-Bromopyruvate boosts the effect of chemotherapy in acute myeloid leukemia by a pro-oxidant mechanismeng
dc.typeresearch article
dspace.entity.typePublication
oaire.citation.endPage202
oaire.citation.startPage192
oaire.citation.titleFree Radical Biology and Medicine
oaire.citation.volume234
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85
person.familyNameGranja
person.givenNameSara
person.identifier.ciencia-idC41F-02E4-065E
person.identifier.orcid0000-0001-8717-6751
relation.isAuthorOfPublication06306a95-9c06-47c7-b2e5-5bbf757bec17
relation.isAuthorOfPublication.latestForDiscovery06306a95-9c06-47c7-b2e5-5bbf757bec17

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