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Determination of the Relative Efficacy of Docosahexaenoic Acid and Eicosapentaenoic Acid in Two-Dimensional and Three-Dimensional Cell Culture Models of Human Breast Cancer

  • Author / Creator
    VanderSluis, Laura

  • Omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), decrease breast cancer cell viability. DHA, EPA, and dietary relevant DHA:EPA mixtures have not been systematically investigated in two-dimensional (2D) cell culture models of human breast cancer and compared to three-dimensional (3D) cell culture models, which recapitulate the tumour microenvironment. The overall objectives of this thesis were to use MDA-MB-231 (triple negative (estrogen receptor-, progesterone receptor-, human epidermal growth factor receptor (Her2)-) and SK-BR-3 (Her2+) human breast cancer cells to: 1) determine if differences exist between DHA, EPA, and DHA:EPA mixtures on cell viability, tumour fatty acid composition, and proteins related to cell death and growth pathways in 2D culture and 2) determine if the effects are maintained in 3D culture. In 2D culture, cells were incubated with 100, 150, or 200 µM DHA, EPA, or DHA:EPA mixtures (1:1 or 2:1) with a background fatty acid mixture (oleic/linoleic acid). In MDA-MB-231 cells all treatments decreased cell viability to the same extent at 100 and 150 µM (25-29% and 19-26%, respectively, pDHA, pEPA+DPA, p<0.05). Increases in CD95 death receptor and decreased FADD content (14 and 22%, p<0.05) may explain the effect of EPA. In 3D culture, changes in EPA+DPA and DHA content with n-3 LCPUFA treatments in whole cell fatty acids were consistent with 2D culture. However, there were increases in MDA-MB-231 spheroid growth (26%, p<0.05) and SK-BR-3 aggregate formation (38-62%, p<0.05), suggesting these indices are not appropriate for studying the anti-cancer effects of n-3 LCPUFA established in 2D culture and animal feeding trials. Collectively, this research is important for using n-3 LCPUFA mixtures to target breast cancer tumours.

  • Subjects / Keywords
  • Graduation date
    Fall 2018
  • Type of Item
    Thesis
  • Degree
    Master of Science
  • DOI
    https://doi.org/10.7939/R3RF5KX44
  • License
    Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.