α‐linolenic acid reduces growth in four breast cancer cell lines with varying receptor expression in high and low estrogen environments

Abstract

Breast cancer differs in cell receptors which then determines effective treatments. Alpha‐linolenic acid (ALA)‐rich flaxseed oil reduced estrogen receptor (ER)+ cell growth at low and high estrogen (E2) but its effect is unclear in cells with varying ER, progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). Our objective was to determine in vitro the ALA and E2 effect on growth and membrane lipids of four breast cancer cell lines with varying ER, PR and HER2 status. Cells were treated with 0 – 200uM ALA ± 1nM E2 and tested for growth by trypan blue exclusion method and fatty acids by gas chromatography. Receptor status confirmed by Western Blot: MCF7‐ER+PR+low HER2; BT474‐ER+PR+HER2+, MDA MB 231‐ER‐PR‐low HER2; MDA MB 468‐ER‐PR‐HER2‐. Compared to –E2 control, MCF7 had a significant E2, ALA and interaction effect on growth; other cell lines only had an ALA effect. 50uM and 75uM ALA significantly decreased growth by 14, 48, 31 and 63% and 38, 77, 80 and 78% in MCF7, BT 474, MDA MB231 and MDA MB468, respectively. E2 significantly increased (91.8%) MCF7 growth. Cells showed significant increases (9–25 fold) in % ALA which related to growth. Thus ALA reduces breast cancer cell growth ± E2 at doses as low as 50uM, likely through alteration of lipid composition. It is effective regardless of ER, PR and HER2 status which may be of importance in difficult to treat cancers such as triple negative. Funded by NSERC.Grant Funding Source: NSERC

A review of the functional activities of chia seed and the mechanisms of action related to molecular targets

“…In particular, COX-2 is the key enzyme in the biosynthesis of inflammatory mediators such as prostaglandins and leukotrienes; besides, the NF-κB pathway regulates the expression of pro-inflammatory cytokines (IL-1β, IL-6 and IL-8), anti-inflammatory factor (IL-10), and nitric oxide (NO). 21,27…”

“…In particular, COX-2 is the key enzyme in the biosynthesis of inflammatory mediators such as prostaglandins and leukotrienes; besides, the NF-κB pathway regulates the expression of pro-inflammatory cytokines (IL-1β, IL-6 and IL-8), anti-inflammatory factor (IL-10), and nitric oxide (NO). 21,27 In vitro cell experiments have shown that the ethanol extract of CS has significant lethality on human prostate cancer cells (PC-3), with an IC 50 value of 1.48 ± 0.72 μg mL −1 . 28 The concentrations of TNF-α and IL-10 were the lowest in Wistar rats fed with a CS ground meal; at the same time, compared to the high-fat group, the expression of NF-κB mRNA was relatively decreased after CS meal treatment.…”

“…There is evidence confirming that DHA, the main component of CSO, is produced by the metabolism of ALA. CSO contributes to the expression of nuclear transcription factors, causes damage to tumor cell mitochondria, promotes tumor cell apoptosis, and affects the production and development of cancer cells. 27 ALA and ω-3 fatty acids (DHA and EPA) are capable of inhibiting the growth and proliferation of human breast cancer cells, suppressing the expression of oncogenes (such as the DNA binding protein inhibitor ID1) in MDA-MB-231, MDA-MB-468, MCF-7 and other breast cancer cells, inducing apoptosis of mutant cells, blocking cancer cell proliferation, and boosting the expression of tumor suppressor genes. 27,31 ALA may reduce breast cancer risk by effectively antagonizing prostaglandin E 2 (PGE 2 ) produced by arachidonic acid.…”

“…27 ALA and ω-3 fatty acids (DHA and EPA) are capable of inhibiting the growth and proliferation of human breast cancer cells, suppressing the expression of oncogenes (such as the DNA binding protein inhibitor ID1) in MDA-MB-231, MDA-MB-468, MCF-7 and other breast cancer cells, inducing apoptosis of mutant cells, blocking cancer cell proliferation, and boosting the expression of tumor suppressor genes. 27,31 ALA may reduce breast cancer risk by effectively antagonizing prostaglandin E 2 (PGE 2 ) produced by arachidonic acid. The level of PGE 2 is positively correlated with increased tumorigenic and metastatic potential of human breast cancer cells.…”

“…COX-2 is an inducible enzyme that catalyzes the production of prostaglandins and has been considered as a biomarker for human breast cancer because its expression is positively correlated with the density of breast tumor cells. 27,32 ALA is responsible for the growth inhibition and apoptosis promotion of estrogen positive breast cancer cells, and the apoptosis promotion pathway is sub-G1 accumulation. 33 ALA at a concentration of 50 μM can significantly degrade the transcription level of COX-2 in MDA-MB-231 cells.…”