Por favor, use este identificador para citar o enlazar este ítem: 10.3390/cancers13010102

Título: Acriflavine, a Potent Inhibitor of HIF-1α, Disturbs Glucose Metabolism and Suppresses ATF4-Protective Pathways in Melanoma under Non-Hypoxic Conditions
Fecha de publicación: 31-dic-2020
Editorial: MDPI
Cita bibliográfica: Cancers. Volumen: 13 ,nº: 1, 2020
ISSN: 2072-6694
Materias relacionadas: CDU::5 - Ciencias puras y naturales::57 - Biología::577 - Bioquímica. Biología molecular. Biofísica
Palabras clave: Acriflavine
Glucose metabolism
Oxygen homeostasis
Resumen: Hypoxia-inducible factor (HIF)-1α is constitutively expressed in melanoma cells under normoxic conditions and its elevated expression correlates with the aggressiveness of melanoma tumors. Here, we used acriflavine, a potent inhibitor of HIF-1α dimerization, as a tool to investigate whether HIF-1α-regulated pathways contribute to the growth of melanoma cells under normoxia. We observed that acriflavine differentially modulated HIF-1α-regulated targets in melanoma under normoxic conditions, although acriflavine treatment resulted in over-expression of vascular endothelial growth factor (VEGF), its action clearly downregulated the expression of pyruvate dehydrogenase kinase 1 (PDK1), a well-known target of HIF-1α. Consequently, downregulation of PDK1 by acrifavine resulted in reduced glucose availability and suppression of the Warburg effect in melanoma cells. In addition, by inhibiting the AKT and RSK2 phosphorylation, acriflavine also avoided protective pathways necessary for survival under conditions of oxidative stress. Interestingly, we show that acriflavine targets activating transcription factor 4 (ATF4) for proteasomal degradation while suppressing the expression of microphthalmia-associated transcription factor (MITF), a master regulator of melanocyte development and a melanoma oncogene. Since acriflavine treatment results in the consistent death of melanoma cells, our results suggest that inhibition of HIF-1α function in melanoma could open new avenues for the treatment of this deadly disease regardless of the hypoxic condition of the tumor.
Autor/es principal/es: Martí Díaz, Román
Montenegro Arce, María Fernanda
Cabezas Herrera, Juan
Goding, Colin
Rodríguez López, José Neptuno
Sánchez del Campo Ferrer, Luis
Facultad/Departamentos/Servicios: Facultades, Departamentos, Servicios y Escuelas::Departamentos de la UMU::Bioquímica y Biología Molecular A
Versión del editor: https://doi.org/10.3390/cancers13010102
URI: http://hdl.handle.net/10201/138353
DOI: 10.3390/cancers13010102
Tipo de documento: info:eu-repo/semantics/article
Número páginas / Extensión: 17
Derechos: info:eu-repo/semantics/openAccess
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
Descripción: ©2020. This manuscript version is made available under the CC-BY 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the Published Manuscript version of a Published Work that appeared in final form in Cancers. To access the final edited and published work see https://doi.org/10.3390/cancers13010102
Aparece en las colecciones:Artículos: Bioquímica y Biología Molecular "A"

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