Bergamot natural products eradicate cancer stem cells (CSCs) by targeting mevalonate, Rho-GDI-signalling and mitochondrial metabolism.
Biochim Biophys Acta Bioenerg
; 1859(9): 984-996, 2018 09.
Article
en En
| MEDLINE
| ID: mdl-29626418
ABSTRACT
Here, we show that a 21 mixture of Brutieridin and Melitidin, termed "BMF", has a statin-like properties, which blocks the action of the rate-limiting enzyme for mevalonate biosynthesis, namely HMGR (3-hydroxy-3-methylglutaryl-CoA-reductase). Moreover, our results indicate that BMF functionally inhibits several key characteristics of CSCs. More specifically, BMF effectively i) reduced ALDH activity, ii) blocked mammosphere formation and iii) inhibited the activation of CSC-associated signalling pathways (STAT1/3, Notch and Wnt/beta-catenin) targeting Rho-GDI-signalling. In addition, BMF metabolically inhibited mitochondrial respiration (OXPHOS) and fatty acid oxidation (FAO). Importantly, BMF did not show the same toxic side-effects in normal fibroblasts that were observed with statins. Lastly, we show that high expression of the mRNA species encoding HMGR is associated with poor clinical outcome in breast cancer patients, providing a potential companion diagnostic for BMF-directed personalized therapy.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
6_breast_cancer
/
6_endocrine_disorders
Asunto principal:
Células Madre Neoplásicas
/
Productos Biológicos
/
Aceites de Plantas
/
Neoplasias de la Mama
/
Inhibidores de la Disociación del Nucleótido Guanina rho-Específico
/
Hidroximetilglutaril-CoA Reductasas
/
Ácido Mevalónico
Tipo de estudio:
Prognostic_studies
Límite:
Female
/
Humans
Idioma:
En
Revista:
Biochim Biophys Acta Bioenerg
Año:
2018
Tipo del documento:
Article