Low carbohydrate diet prevents Mcl-1-mediated resistance to BH3-mimetics.
Oncotarget
; 7(45): 73270-73279, 2016 11 08.
Article
en En
| MEDLINE
| ID: mdl-27689327
ABSTRACT
Overexpression of Mcl-1 is implicated in resistance of several cancers to chemotherapeutic treatment, therefore identifying a safe way to decrease its expression in tumor cells represents a central goal. We investigated if a modulation of the diet could impact on Mcl-1 expression using a Myc-driven lymphoma model. We established that a partial reduction of caloric intake by 25% represents an efficient way to decrease Mcl-1 expression in tumor cells. Furthermore, using isocaloric custom diets, we observed that carbohydrates (CHO) are the main regulators of Mcl-1 expression within the food. Indeed, feeding lymphoma-bearing mice with a diet having 25% less carbohydrates was sufficient to decrease Mcl-1 expression by 50% in lymphoma cells. We showed that a low CHO diet resulted in AMPK activation and mTOR inhibition leading to eukaryotic elongation factor 2 (eEF2) inhibition, blocking protein translation elongation. Strikingly, a low CHO diet was sufficient to sensitize Myc-driven lymphoma-bearing mice to ABT-737-induced cell death in vivo. Thus reducing carbohydrate intake may represent a safe way to decrease Mcl-1 expression and to sensitize tumor cells to anti-cancer therapeutics.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Fragmentos de Péptidos
/
Proteínas Proto-Oncogénicas
/
Dieta Baja en Carbohidratos
/
Proteína 1 de la Secuencia de Leucemia de Células Mieloides
/
Mimetismo Biológico
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Oncotarget
Año:
2016
Tipo del documento:
Article
País de afiliación:
Francia