N-3 Polyunsaturated fatty acid ethyl esters decrease the invasion, but not the proliferation, of human colorectal cancer cells via a PI3K-dependent mechanism in vitro

Prostaglandins Leukot Essent Fatty Acids. 2021 Apr:167:102273. doi: 10.1016/j.plefa.2021.102273. Epub 2021 Mar 24.

Abstract

N-3 polyunsaturated fatty acid (PUFA) ethyl esters have been approved by the FDA for the treatment of dyslipidemia and are promising cancer therapeutics. The study objectives were to determine if and how n-3 PUFA ethyl esters affected the proliferation and invasion of colorectal cancer cells. SW620 and HCT-116 parental and HCT-116 mutant cells isogenic for constitutively active PI3K were treated with free or ethyl esterified n-3 PUFAs and counted 72 h later. Cells were also administered n-3 PUFA ethyl esters to determine if these compounds decreased invasion through Boyden chambers and PI3K activity via western blot analysis of phosphorylated Akt. Free and n-3 PUFA ethyl esters decreased the proliferation of all cell lines. The invasion and Akt phosphorylation of both parental cell lines was decreased following treatment but this did not occur in mutant cells. The ability of n-3 PUFA ethyl esters to decrease proliferation and invasion in vitro indicates these compounds may be effective in vivo.

Keywords: Colorectal cancer; Metastasis; N-3 polyunsaturated fatty acids; Phosphatidylinositol 3-kinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Cell Proliferation / drug effects
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Esterification
  • Esters / pharmacology*
  • Fatty Acids, Omega-3 / chemistry
  • Fatty Acids, Omega-3 / pharmacology*
  • Humans
  • Neoplasm Invasiveness
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphorylation
  • Tumor Cells, Cultured

Substances

  • Esters
  • Fatty Acids, Omega-3