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The objective of this work is to evaluate the influence of pomegranate peel extract (PPE) in the behavior of breast cell lines (epithelial and tumor type) and related oxidative metabolism. Fruit-based functional foods have been the target of increasing scientific research for their physiological and pathophysiological properties. Pomegranate (Punica granatum) is a suitable example with both prophylactic and medicinal effects. MCF-7 cell line from tumor breast carcinoma, and MCF-10A cell line from normal epithelial mammary gland were used and subjected to different concentrations of PPE, ranging from 1 to 5 mM of gallic acid equivalents (GAE). Viability, proliferation, mobility, and cytotoxicity assays were performed along with the quantification of antioxidant enzymes, namely, catalase, superoxide dismutase (SOD) and reduced (GSH) and oxidized (GSSG) glutathione. We observed a decrease in viability and proliferation of MCF-7 cells, at higher concentrations of PPE, with no influence in epithelial cells. Interestingly, in a concentration-dependent manner, PPE triggered a significant decrease in migration on both cell lines, with a more pronounced effect in breast cancer cell line. Regarding antioxidant enzyme activity, on tumor cells higher concentrations of PPE decreased catalase activity and significantly increased SOD activity. Regarding GSH and GSSG, we observed different expression levels between MCF-7 and MCF-10A, with MCF-7 presenting lower levels compared to MCF-10A. GSH/GSSG ratio was notably higher in MCF-7 at 5 mM GAE. PPE exhibits anti-tumor effects without significantly affecting normal epithelial cells. Our work strengthens the potential antitumoral effect of PPE by reducing MCF-7 cell viability and proliferation through the imbalance of antioxidant enzymes. [ABSTRACT FROM AUTHOR]

It is well established that tumour cells undergo metabolic changes to acquire biological advantage over normal cells with activation of the glycolytic pathway, a process termed "Warburg effect". Enzyme isoforms are alternative enzymatic forms with the same function but with different biochemical or epigenetic features. Moreover, isoforms may have varying impacts on different metabolic pathways. We challenge ourselves to analyse the glycolytic and gluconeogenic enzymes and isoforms in breast cancer, a complex and heterogeneous pathology, associated with high incidence and mortality rates especially among women. We analysed epithelial and tumour cell lines by RT-PCR and compared values to a publicly available database for the expression profile of normal and tumour tissues (Gepia) of enzymes and enzymatic isoforms from glycolytic and gluconeogenic pathways. Additionally, GeneMANIA was used to evaluate interactions, pathways, and attributes of each glycolytic/gluconeogenic steps. The findings reveal that the enzymes and enzymatic isoforms expressed in cell culture were somewhat different from those in breast tissue. We propose that the tumor microenvironment plays a crucial role in the expression of glycolytic and gluconeogenic enzymes and isoforms in tumour cells. Nonetheless, they not only participate in glycolytic and gluconeogenic enzymatic activities but may also influence other pathways, such as the Pentose-Phosphate-Pathway, TCA cycle, as well as other carbohydrate, lipid, and amino acid metabolism. [Display omitted] • Enzymatic isoforms may have varying impacts on different metabolic pathways. • Enzymatic isoforms expressed differently in cell culture from breast cancer tissue. • Glycolysis and gluconeogenic enzymatic isoforms present a distinct expression. [ABSTRACT FROM AUTHOR]