title: Bergapten induces metabolic reprogramming in breast cancer cells.
abstract: Alterations in cellular metabolism are among the most consistent hallmarks of cancer. Herein, after a comprehensive metabolic phenotype characterization of MCF7 and ZR75 breast cancer cells, we investigated the activity of bergapten (Bg), a plant-derived compound, against breast cancer. The study of different biochemical pathways involved in cell metabolism revealed that the two cell lines have different bioenergetic phenotypes: MCF7 cells express a glycolytic phenotype only partially oxidative, while ZR75 cells mainly have an oxidative phenotype. In both cell lines, Bg blocked glycolysis and significantly decreased glucose-6-phosphate dehydrogenase (G6PDH) activity promoting glucose accumulation; modulated bioenergetic requirements altering the expression of oxidative phosphorylation (OXPHOS) complexes and ATP production; and induced a lipid-lowering effect since an increased lipase activity concomitantly to a reduction in triglyceride levels was observed. Quantitative data of different metabolites and enzymatic activities were presented. Treatment with Bg resulted in an alteration in different metabolic pathways inducing death in the cells. We report a novel action of the natural product Bg on breast cancer, since it induced metabolic reprogramming by disrupting the interconnected network of different metabolic mechanisms. Bg can be used in combination with other forms of targeted chemotherapy to improve cancer treatment outcomes.
authors.affiliation: Centro Sanitario, University of Calabria, I-87030 Arcavacata di Rende (CS), Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Santoro
authors.affiliation: Centro Sanitario, University of Calabria, I-87030 Arcavacata di Rende (CS), Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Guido
authors.affiliation: Centro Sanitario, University of Calabria, I-87030 Arcavacata di Rende (CS), Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: De Amicis
authors.affiliation: Centro Sanitario, University of Calabria, I-87030 Arcavacata di Rende (CS), Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Sisci
authors.affiliation: Department of Pharmacy and Science of Health and Nutrition, University of Calabria, I-87030 Arcavacata di Rende (CS), Italy.
authors.forename: Erika
authors.initials: E
authors.lastname: Cione
authors.affiliation: Department of Pharmacy and Science of Health and Nutrition, University of Calabria, I-87030 Arcavacata di Rende (CS), Italy.
authors.forename: Dolce
authors.initials: D
authors.lastname: Vincenza
authors.affiliation: Centro Sanitario, University of Calabria, I-87030 Arcavacata di Rende (CS), Italy.
authors.forename: Ada
authors.initials: A
authors.lastname: Donà
authors.affiliation: Department of Pharmacy and Science of Health and Nutrition, University of Calabria, I-87030 Arcavacata di Rende (CS), Italy.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Panno
authors.affiliation: Centro Sanitario, University of Calabria, I-87030 Arcavacata di Rende (CS), Italy.
authors.forename: Saveria
authors.initials: S
authors.lastname: Aquila
mesh_terms: D000078223:5-Methoxypsoralen; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects*; D006801:Humans; D008049:Lipase / Q000378:metabolism; D061986:MCF-7 Cells; D008730:Methoxsalen / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000078223:5-Methoxypsoralen; D005954:Glucosephosphate Dehydrogenase; D008049:Lipase; D008730:Methoxsalen