Artículo
Glucose 6-phosphate dehydrogenase inhibition sensitizes melanoma cells to metformin treatment
Arbe, María Florencia
; Agnetti, Lucrecia
; Breininger, Elizabeth
; Glikin, Gerardo Claudio
; Finocchiaro, Liliana Maria Elena
; Villaverde, Marcela Solange
Fecha de publicación:
11/2020
Editorial:
Neoplasia Press
Revista:
Translational Oncology
ISSN:
1936-5233
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Most cancer cells exacerbate the pentose phosphate pathway (PPP) to enhance biosynthetic precursors and antioxidant defenses. Metformin, which is used as a first-line oral drug for the treatment of type 2 diabetes, has been proposed to inhibit the malignant progression of different types of cancers. However, metformin has shown poor efficacy as single agent in several clinical trials. Thus, the aim of the present work was to investigate whether the pharmacological inhibition of G6PDH, the first and rate-limiting enzyme of the PPP, by 6-amino nicotinamide (6-AN) potentiates the antitumoral activity of metformin on different human melanoma cell lines. Our results showed that 6-AN has sensitizing properties to metformin cytotoxicity. The combination of metformin and 6-AN decreased glucose consumption and lactate production, altered the mitochondrial potential and redox balance, and thereby blocked melanoma cell progression, directing cells to apoptosis and necrosis. To our knowledge, this is the first study describing the effect of this combination. Future preclinical studies should be performed to reveal the biological relevance of this finding.
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Articulos(INPA)
Articulos de UNIDAD EJECUTORA DE INVESTIGACIONES EN PRODUCCION ANIMAL
Articulos de UNIDAD EJECUTORA DE INVESTIGACIONES EN PRODUCCION ANIMAL
Articulos(OCA HOUSSAY)
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Citación
Arbe, María Florencia; Agnetti, Lucrecia; Breininger, Elizabeth; Glikin, Gerardo Claudio; Finocchiaro, Liliana Maria Elena; et al.; Glucose 6-phosphate dehydrogenase inhibition sensitizes melanoma cells to metformin treatment; Neoplasia Press; Translational Oncology; 13; 11; 11-2020; 1-11
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