Anti-proliferative effects of a new docosapentaenoic acid monoacylglyceride in colorectal carcinoma cells

Prostaglandins Leukot Essent Fatty Acids. 2013 Sep;89(4):203-13. doi: 10.1016/j.plefa.2013.07.004. Epub 2013 Aug 7.

Abstract

N-3 polyunsaturated fatty acids (n-3 PUFAs) have been shown to inhibit the induction and progression of many tumor types. However, the anticancer effect of n-3 PUFA monoglyceride on colorectal cancer has yet to be assessed. The aim of the present study was to determine the anti-tumorigenic effects of docosahexaenoic acid monoglyceride (MAG-DHA), eicosapentaenoic acid monoglyceride (MAG-EPA) and docosapentaenoic acid (22:5n-3) monoglyceride (MAG-DPA) in colorectal carcinoma cells. Our results demonstrate that MAG-DHA, MAG-EPA and MAG-DPA all decreased cell proliferation and induced apoptosis in HCT116 cells, with MAG-DPA having the higher anti-proliferative and pro-apoptotic effects in vitro. In a HCT116 xenograft mouse model, oral administration of MAG-DPA significantly inhibited tumor growth. Furthermore, MAG-DPA treatments decreased NFκB activation leading to a reduction in Bcl-2, CyclinD1, c-myc, COX-2, MMP9 and VEGF expression levels in tumor tissue sections. Altogether, these data provide new evidence regarding the mode of action of MAG-DPA in colorectal cancer cells.

Keywords: Apoptosis; Colorectal carcinoma; DPA; NFκB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Caspase 3 / metabolism
  • Cell Proliferation / drug effects*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / metabolism
  • Drug Synergism
  • Fatty Acids / metabolism
  • Female
  • HCT116 Cells
  • Humans
  • Inhibitory Concentration 50
  • Lipid Metabolism / drug effects
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Mice, Nude
  • Monoglycerides / metabolism
  • Monoglycerides / pharmacology*
  • NF-kappa B / metabolism
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Vascular Endothelial Growth Factor A / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • 1-O-docosapentaenoylglycerol
  • 1-eicosapentaenoylglycerol
  • Antineoplastic Agents
  • Fatty Acids
  • Monoglycerides
  • NF-kappa B
  • Platelet Endothelial Cell Adhesion Molecule-1
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • docosahexaenoic acid monoacylglyceride
  • CASP3 protein, human
  • Caspase 3
  • MMP9 protein, human
  • Matrix Metalloproteinase 9