Differential Response of Two Human Breast Cancer Cell Lines to the Phenolic Extract from Flaxseed Oil.

Key Findings

The objective of this study was to characterize the phenolic extract from flaxseed (FS) oil, and to assess its potential effects on two human breast cancer cell lines, MCF7 and MDA-MB231, and on the human non-cancerous breast cell line, MCF10A, in terms of cell growth, cell death, cell cycle, cell signaling, and lipid peroxidation. The study also evaluated and correlated by a network analysis the expression of some genes known for their pro-oxidant properties. The results showed that the extract acts as a metabolic probe highlighting the differences between the two different cell types of breast cancer. The phenolic extract was very effective on the cancerous estrogen-receptor-positive MCF7 cell line by inducing: (1) a significant decrease of cell proliferation with a simultaneous increase of apoptosis and of the cell cycle G0/G1 phase when compared to untreated cells; (2) an evident activation of the H2AX signaling but not of that of PI3K; (3) an increase of lipid peroxidation; and (4) the up-regulation of CYP1A1, IL-1β, IL-6, iNOS genes, and also of genes corresponding to two subunits of NF-κB. On the estrogen-receptor-negative MDA-MB2131 cells: (1) only an anti-proliferative activity; (2) a weak lipid peroxidation and the PI3K signaling pathway activation; and (3) an up-regulation of CYP1A1, of the anti-apoptotic NF-κB and of two GPXs. There was a strong pro-oxidant effect of this phenolic extract, exerted only on the cancerous estrogen-receptor-positive MCF7 cell line through the increase of lipid peroxidation.

Abstract

Many studies have evidenced that the phenolic components from flaxseed (FS) oil have potential health benefits. The effect of the phenolic extract from FS oil has been evaluated on two human breast cancer cell lines, MCF7 and MDA-MB231, and on the human non-cancerous breast cell line, MCF10A, by SRB assay, cellular death, cell cycle, cell signaling, lipid peroxidation and expression of some key genes. We have evidenced that the extract shows anti-proliferative activity on MCF7 cells by inducing cellular apoptosis, increase of the percentage of cells in G0/G1 phase and of lipid peroxidation, activation of the H2AX signaling pathway, and upregulation of a six gene signature. On the other hand, on the MDA-MB2131 cells we verified only an anti-proliferative activity, a weak lipid peroxidation, the activation of the PI3K signaling pathway and an up-regulation of four genes. Overall these data suggest that the extract has both cytotoxic and pro-oxidant effects only on MCF7 cells, and can act as a metabolic probe, inducing differences in the gene expression. For this purpose, we have performed an interactomic analysis, highlighting the existing associations. From this approach, we show that the phenotypic difference between the two cell lines can be explained through their differential response to the phenolic extract.