Growth and gene expression differ over time in alpha-linolenic acid treated breast cancer cells

Exp Cell Res. 2015 Apr 10;333(1):147-54. doi: 10.1016/j.yexcr.2015.02.020. Epub 2015 Mar 2.


Scope: Heterogeneity of breast cancer (BC) subtypes makes BC treatment difficult. α-linolenic acid (ALA), rich in flaxseed oil, has been shown to reduce growth and increase apoptosis in several BC cell lines, but the mechanism of action needs further understanding.

Methods and results: Four BC cell lines (MCF-7, BT-474, MDA-MB-231 and MDA-MB-468) were incubated with 75 μM ALA+1 nM 17-β estradiol (E2) or 1 nM E2 only (control) for 24 h. MDA-MB-231 cells were additionally incubated at 6 and 12 h. Viable cell number was measured, and expression of genes related to BC (signaling pathways, cell cycle, apoptosis) was quantified by real-time PCR array. There was a reduction in growth of all ALA treated cell lines after 24 h, and in MDA-MB-231 cells this was time-dependent. Many genes were altered after 24 h, and these differed between cell lines. In MDA-MB-231 cells, several gene expression changes were time-dependent.

Conclusions: ALA reduces growth of BC cell lines, by modifying signaling pathways, which differ between BC molecular subtypes. The ALA effect on gene expression is dynamic and changes over time, indicating the significance of incubation period in detecting gene changes.

Keywords: Alpha-linolenic acid; Breast cancer; Gene expression; Molecular subtype; Time effect; n-3 PUFA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism
  • Breast Neoplasms
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Proliferation / drug effects
  • Drug Screening Assays, Antitumor
  • Female
  • Gene Expression / drug effects
  • Humans
  • MCF-7 Cells
  • alpha-Linolenic Acid / pharmacology*


  • Antineoplastic Agents
  • Apoptosis Regulatory Proteins
  • Cell Cycle Proteins
  • alpha-Linolenic Acid