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Abstract Title:

Bergamot natural products eradicate cancer stem cells (CSCs) by targeting mevalonate, Rho-GDI-signalling and mitochondrial metabolism.

Abstract Source:

Biochim Biophys Acta Bioenerg. 2018 09 ;1859(9):984-996. Epub 2018 Apr 4. PMID: 29626418

Abstract Author(s):

Marco Fiorillo, Maria Peiris-Pagès, Rosa Sanchez-Alvarez, Lucia Bartella, Leonardo Di Donna, Vincenza Dolce, Giovanni Sindona, Federica Sotgia, Anna Rita Cappello, Michael P Lisanti

Article Affiliation:

Marco Fiorillo

Abstract:

Here, we show that a 2:1 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.

Study Type : In Vitro Study

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Sayer Ji
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