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

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

doi:10.1016/j.bbabio.2018.03.018

Cited by 58 publications

(39 citation statements)

References 57 publications

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“…As mentioned above, treatment with various statins targeting CSC self-renewal resulted in elimination of CSCs in breast [34] and brain [86] cancers. Moreover, a mixture of brutieridin and melitidin, which has statin-like properties, eradicates CSCs by targeting mevalonate, Rho-GDI-signaling, and mitochondrial metabolism [123]. In addition, bergamot metabolically inhibits OXPHOS and FAO [123].…”

Section: Cholesterol Synthesis Through the Mevalonate Pathwaymentioning

confidence: 99%

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Crosstalk between autophagy and metabolic regulation of cancer stem cells

et al. 2020

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Cancer is now considered as a heterogeneous ecosystem in which tumor cells collaborate with each other and with host cells in their microenvironment. As circumstances change, the ecosystem evolves to ensure the survival and growth of the cancer cells. In this ecosystem, metabolism is not only a key player but also drives stemness. In this review, we first summarize our current understanding of how autophagy influences cancer stem cell phenotype. We emphasize metabolic pathways in cancer stem cells and discuss how autophagy-mediated regulation metabolism is involved in their maintenance and proliferation. We then provide an update on the role of metabolic reprogramming and plasticity in cancer stem cells. Finally, we discuss how metabolic pathways in cancer stem cells could be therapeutically targeted.

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Section: Cholesterol Synthesis Through the Mevalonate Pathwaymentioning

confidence: 99%

“…Moreover, a mixture of brutieridin and melitidin, which has statin-like properties, eradicates CSCs by targeting mevalonate, Rho-GDI-signaling, and mitochondrial metabolism [123]. In addition, bergamot metabolically inhibits OXPHOS and FAO [123].…”

Section: Cholesterol Synthesis Through the Mevalonate Pathwaymentioning

confidence: 99%

Crosstalk between autophagy and metabolic regulation of cancer stem cells

et al. 2020

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“…CIC is involved in many important biochemical pathways, including gluconeogenesis, insulin secretion, inflammation [ 43 , 44 , 45 , 46 ], protein acetylation [ 45 , 47 , 48 ] and innate immune cell function [ 45 ]. Additionally, its activity is decreased during chronic cholestasis [ 49 ], and its inhibition might be useful in nonalcoholic fatty liver disease [ 50 ], as well as in cancer resistance [ 51 , 52 , 53 ] and in apoptosis induction in cancer cells [ 54 ]. The expression of the human CIC (hCIC) is very high in the liver, but this carrier is also expressed in the pancreas and kidney [ 3 ].…”

Section: Drosophila Melanogaster Vs Human Mitomentioning

confidence: 99%

Drosophila melanogaster Mitochondrial Carriers: Similarities and Differences with the Human Carriers

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Lunetti

Zara

et al. 2020

IJMS

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Mitochondrial carriers are a family of structurally related proteins responsible for the exchange of metabolites, cofactors and nucleotides between the cytoplasm and mitochondrial matrix. The in silico analysis of the Drosophila melanogaster genome has highlighted the presence of 48 genes encoding putative mitochondrial carriers, but only 20 have been functionally characterized. Despite most Drosophila mitochondrial carrier genes having human homologs and sharing with them 50% or higher sequence identity, D. melanogaster genes display peculiar differences from their human counterparts: (1) in the fruit fly, many genes encode more transcript isoforms or are duplicated, resulting in the presence of numerous subfamilies in the genome; (2) the expression of the energy-producing genes in D. melanogaster is coordinated from a motif known as Nuclear Respiratory Gene (NRG), a palindromic 8-bp sequence; (3) fruit-fly duplicated genes encoding mitochondrial carriers show a testis-biased expression pattern, probably in order to keep a duplicate copy in the genome. Here, we review the main features, biological activities and role in the metabolism of the D. melanogaster mitochondrial carriers characterized to date, highlighting similarities and differences with their human counterparts. Such knowledge is very important for obtaining an integrated view of mitochondrial function in D. melanogaster metabolism.

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“…Almost always and in both the juice and the cloudy of the three cvs of bergamot, the neohesperidin content was highest in Fantastico (Tables 4-5). Brutieridin and melitidin are two molecules identified and described in the bergamot juice by Di Donna et al [30][31][32][33] and Fiorillo et al [34]. The name brutieridin comes from the ancient name of one of the Calabrian cities (Brutium, today Cosenza) where brutieridin and melitidin were studied, whereas melitidin derives from the name of one of the most important towns (Melito Porto Salvo) where the bergamot tree is cultivated.…”

Section: Flavonoidsmentioning

confidence: 99%

Bergamot (<em>Citrus bergamia</em>, Risso): The Effects of Cultivar and Harvest Date on Functional Properties of Juice and Cloudy

Giuffré¹

2019

Preprint

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Reggio Calabria province (South Italy) is known for being almost the only area of cultivation of the bergamot fruit, grown principally for its essential oil, but today much studied for the health benefits of its juice. The biometrics and physico-chemical properties of the three (Citrus bergamia Risso) existing genotypes namely Castagnaro, Fantastico and Femminello were studied during fruit ripening from October to March. Castagnaro cv had the biggest and heaviest fruit during this harvest period. °Brix (7.9-10.0), pH (2.2-2.8) and Formol number (1.47-2.37 mL NaOH 0.1N/100mL) were shown to be influenced by both the genotype and by the harvest date. Titratable acidity (34.98-59.50 g/L) and Vitamin C (Ascorbic acid) (341-867 g/L) decreased during fruit ripening. The evolution of flavonoids such as neoeriocitrin, naringin, neohesperidin brutieridin and melitidin was studied both in bergamot juice and in the bergamot cloudy which is the aqueous extract of bergamot during fruit processing. Bergamot cloudy contained a higher quantity of flavonoids compared to the juice. This study gives important information regarding the cultivar and the harvest date for producers who want to obtain the highest juice quantity or the highest juice quality from the bergamot fruit.

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

Cited by 58 publications

References 57 publications

Crosstalk between autophagy and metabolic regulation of cancer stem cells

Crosstalk between autophagy and metabolic regulation of cancer stem cells

Drosophila melanogaster Mitochondrial Carriers: Similarities and Differences with the Human Carriers

Bergamot (<em>Citrus bergamia</em>, Risso): The Effects of Cultivar and Harvest Date on Functional Properties of Juice and Cloudy

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