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Bergamot natural products eradicate cancer stem cells (CSCs) by targeting mevalonate, Rho-GDI-signalling and mitochondrial metabolism.
Fiorillo, Marco; Peiris-Pagès, Maria; Sanchez-Alvarez, Rosa; Bartella, Lucia; Di Donna, Leonardo; Dolce, Vincenza; Sindona, Giovanni; Sotgia, Federica; Cappello, Anna Rita; Lisanti, Michael P.
Afiliação
  • Fiorillo M; Paterson Institute, University of Manchester, Withington M20 4BX, United Kingdom; Translational Medicine, School of Environment and Life Sciences, Biomedical Research Centre (BRC), University of Salford, Greater Manchester M5 4WT, United Kingdom; The Department of Pharmacy, Health and Nutritional Sc
  • Peiris-Pagès M; Paterson Institute, University of Manchester, Withington M20 4BX, United Kingdom.
  • Sanchez-Alvarez R; Paterson Institute, University of Manchester, Withington M20 4BX, United Kingdom.
  • Bartella L; The Department of Chemistry and Chemical Technologies (CTC) of the University of Calabria, Cosenza, Italy.
  • Di Donna L; The Department of Chemistry and Chemical Technologies (CTC) of the University of Calabria, Cosenza, Italy.
  • Dolce V; The Department of Pharmacy, Health and Nutritional Sciences, The University of Calabria, Cosenza, Italy.
  • Sindona G; The Department of Chemistry and Chemical Technologies (CTC) of the University of Calabria, Cosenza, Italy.
  • Sotgia F; Paterson Institute, University of Manchester, Withington M20 4BX, United Kingdom; Translational Medicine, School of Environment and Life Sciences, Biomedical Research Centre (BRC), University of Salford, Greater Manchester M5 4WT, United Kingdom. Electronic address: fsotgia@gmail.com.
  • Cappello AR; The Department of Pharmacy, Health and Nutritional Sciences, The University of Calabria, Cosenza, Italy. Electronic address: annarita.cappello@unical.it.
  • Lisanti MP; Paterson Institute, University of Manchester, Withington M20 4BX, United Kingdom; Translational Medicine, School of Environment and Life Sciences, Biomedical Research Centre (BRC), University of Salford, Greater Manchester M5 4WT, United Kingdom. Electronic address: M.P.Lisanti@salford.ac.uk.
Biochim Biophys Acta Bioenerg ; 1859(9): 984-996, 2018 09.
Article em 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.
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Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Células-Tronco Neoplásicas / Produtos Biológicos / Óleos de Plantas / Neoplasias da Mama / Inibidores da Dissociação do Nucleotídeo Guanina rho-Específico / Hidroximetilglutaril-CoA Redutases / Ácido Mevalônico Tipo de estudo: Prognostic_studies Limite: Female / Humans Idioma: En Revista: Biochim Biophys Acta Bioenerg Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Células-Tronco Neoplásicas / Produtos Biológicos / Óleos de Plantas / Neoplasias da Mama / Inibidores da Dissociação do Nucleotídeo Guanina rho-Específico / Hidroximetilglutaril-CoA Redutases / Ácido Mevalônico Tipo de estudo: Prognostic_studies Limite: Female / Humans Idioma: En Revista: Biochim Biophys Acta Bioenerg Ano de publicação: 2018 Tipo de documento: Article