Omega-3 free fatty acids attenuate insulin-promoted breast cancer cell proliferation

Nutr Res. 2017 Jun:42:43-50. doi: 10.1016/j.nutres.2017.04.008. Epub 2017 May 4.

Abstract

High insulin levels in obese people are considered as a risk factor to induce breast carcinogenesis. And consumption of fish oils which mainly contain omega-3 fatty acids is associated with a reduced risk of breast cancer. However, whether omega-3 free fatty acids (FFAs) modulate insulin signaling pathway to prevent breast cancer is poorly understood. The current study tested the hypothesis that omega-3 FFAs attenuate insulin-induced breast cancer cell proliferation and regulate insulin signaling pathway. We show here that omega-3 FFAs attenuate MCF-7 cell proliferation and Akt and Erk1/2 phosphorylation levels stimulated by insulin. Knockdown Shp2 by siRNA resulted in significantly elevated omega-3 FFAs-activated Akt phosphorylation but failed to change insulin-stimulated Akt and Erk1/2 phosphorylation. And viable cell number was not affected by either downregulation of Shp2 expression or Erk1/2 inhibitor U0126 treatment. These observations indicated that omega-3 FFAs attenuate insulin-promoted breast cancer cell proliferation and insulin-activated Akt phosphorylation.

Keywords: Breast cancer; Insulin; Insulin signal pathway; Omega-3 free fatty acids; shp2.

MeSH terms

  • Breast Neoplasms / pathology*
  • Butadienes / pharmacology
  • Cell Proliferation / drug effects*
  • Fatty Acids, Omega-3 / pharmacology*
  • Female
  • Gene Expression Regulation
  • Humans
  • Insulin / adverse effects*
  • MCF-7 Cells
  • Mitogen-Activated Protein Kinases / genetics
  • Mitogen-Activated Protein Kinases / metabolism
  • Nitriles / pharmacology
  • Phosphorylation
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11 / genetics
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11 / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction

Substances

  • Butadienes
  • Fatty Acids, Omega-3
  • Insulin
  • Nitriles
  • U 0126
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinases
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11