α-Linolenic Acid Reduces Growth of Both Triple Negative and Luminal Breast Cancer Cells in High and Low Estrogen Environments

Abstract

Flaxseed, rich in α-linolenic acid (ALA), is a complementary breast cancer (BC) therapy; however ALA effectiveness and mechanism are unclear. Variation in cellular expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and estrogen (E2) levels may alter ALA effectiveness. This research determined the effect of ALA on growth, apoptosis, and phospholipid fatty acids of 4 BC cell lines with varying receptor expression ± E2. MCF-7 (ER+/PR+/HER2-), BT-474 (ER+/PR+/HER2+), MDA-MB-231 (ER-/PR-/HER2-) and MDA-MB-468 (ER-/PR-/HER2-) cells were incubated with ALA (50-200 μM) ± 1 nM E2 for 48-72 h. ALA dose-dependently reduced growth, measured by trypan blue exclusion, of all cells (55-80% with 75 μM), and this effect was not altered by E2. ALA (75 μM)+E2 induced apoptosis, measured by flow cytometry (up to 111.2%). Decreased growth and increased apoptosis is related to increased cell phospholipid % ALA (up to 25.1%), measured by gas chromatography. ALA is shown for the first time to reduce cell growth and induce apoptosis regardless of receptor expression and E2 environment, by incorporating into BC phospholipids, supporting the use of ALA and ALA-rich foods as a safe, inexpensive complementary therapy for a wide range of BC.

H2S-releasing nanoemulsions: a new formulation to inhibit tumor cells proliferation and improve tissue repair

“…Our results are in agreement with recent studies where ALA treatment (75 μM, 72 h) reduces the cell growth of MCF-7 cells [124]. The authors suggests that ALA affects cell cycle, grow factors signaling, oxidative stress, anti-estrogenic activity or RNA/micro RNA expression [124].…”

“…The authors suggests that ALA affects cell cycle, grow factors signaling, oxidative stress, anti-estrogenic activity or RNA/micro RNA expression [124]. Additionally, ALA may be incorporated in lipid rafts of the cell membrane, affecting cell signaling and growth [124–126]. …”

Aspirin and metformin exhibit antitumor activity in murine breast cancer

“…Triple-negative breast cancer cell lines [i.e., lacking the estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2 (HER2)] are less affected by estrogen than traditional cell lines (37,38). Accordingly, estrogen suppression treatment is usually not recommended in such cases, including in 4T1 cells.…”

A Combination of Curcumin from Turmeric and Alpha-linolenic Acid Shows Antagonism with MCF-7 Breast Cancer Cells in Phenol-red Free Medium

“…The number of reports dealing with the effect of ALA on MCF-7 cells is limited at present [15,[31][32][33]. There was a 55% inhibition of MCF-7 cells exposed to 75 µM ALA for 2 days in phenol redfree medium [31] and treatment with 50 µM of ALA produced 33% inhibition [32].…”