alpha linolenic acid reduces the growth of HER2overexpressing breast cancer cells that are sensitive or resistant to trastuzumab (TRAS) and prevents TRAS resistance development

January 1, 2014 Human Health and Nutrition Data 0 Comments

alpha linolenic acid reduces the growth of HER2overexpressing breast cancer cells that are sensitive or resistant to trastuzumab (TRAS) and prevents TRAS resistance development

Year: 2014
Authors: Mason, J.
Publication Name: ISSFAL International Congress, Stockholm, Sweden June 28 – July 1
Publication Details: ID# Sunday M7.12

Abstract:

Background: TRAS is used to treat HER2 plus breast cancer but a major problem is resistance. Many breast cancer patients consume alpha linolenic acid (ALA) rich foods; whether ALA reduces HER2 plus breast cancer growth, interacts with TRAS, and prevents TRAS resistance development is unclear. Objectives: To determine the effect of ALA alone and combined with TRAS throughout the progression from TRAS sensitivity to resistance on growth of HER2 plus breast cancer cells (BT474) and to explore mechanisms of effect. Methods: For 12 weeks, BT474 cells were cultured under standard conditions (Parental), with TRAS (10 microg/ml) alone (HR1), or with both TRAS and 25 microM ALA (HR2). Sensitivity to TRAS (0100  microg/ml) was measured by MTS assay at week 12. Cell lines (Parental, HR1, HR2) were treated with TRAS (10  microg/ml), ALA (50 and 100 microM) and their combination for 72 hours and cell growth was measured by trypan blue. Phospholipid fatty acids, apoptosis, and gene and protein signaling biomarker expressions were measured in Control, ALA, TRAS and ALA plus TRAS treated Parental and HR1 cells. Results: At week 12, TRAS caused no effect in HR1 cells indicating resistance, but inhibited parental and HR2 cell growth. ALA significantly lowered the growth of all cell lines with 3059 percent  reductions in cells treated with ALA (100  microM) with and without TRAS vs. TRAS alone or control cells, respectively. ALA significantly altered phospholipid fatty acids (50 and 81 fold higher ALA, 2 and 1.8 fold lower EPA, 1.9 and 2.2 fold lower DHA in Parental and HR1 cells, respectively). ALA induced apoptosis in HR1 but not Parental cells. ALA affected the expression of various gene and protein biomarkers with greater effects seen in HR1 cells. Conclusion: ALA reduces the growth of both TRAS sensitive and resistant HER2 plus cells and prevents TRAS resistance development. Mechanisms involve modulation of the phospholipid fatty acid profile. (Authors abstract)



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