Bergapten induces metabolic reprogramming in breast cancer cells

Santoro,Marta; Guido,Carmela; De Amicis,Francesca; Sisci,Diego; Cione,Erika; Dolce,Vincenza; Donà,Ada; Panno,Maria  Luisa; Aquila,Saveria

doi:10.3892/or.2015.4327

Bergapten induces metabolic reprogramming in breast cancer cells

Authors:
- Marta Santoro
- Carmela Guido
- Francesca De Amicis
- Diego Sisci
- Erika Cione
- Vincenza Dolce
- Ada Donà
- Maria Luisa Panno
- Saveria Aquila
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Affiliations: Centro Sanitario, University of Calabria, I-87030 Arcavacata di Rende (CS), Italy, Department of Pharmacy and Science of Health and Nutrition, University of Calabria, I-87030 Arcavacata di Rende (CS), Italy
Published online on: October 8, 2015 https://doi.org/10.3892/or.2015.4327
Pages: 568-576

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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.

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