Effect of an omega-3 fatty acid containing lipid emulsion alone and in combination with 5-fluorouracil (5-FU) on growth of the colon cancer cell line Caco-2

Eur J Nutr. 2003 Dec;42(6):324-31. doi: 10.1007/s00394-003-0427-1.


Background: In this study we examined the effects of a fish oil-based lipid emulsion (FO) rich in omega-3 fatty acids, which is used in humans as a component of parenteral nutrition, on the growth of the colon cancer cell line Caco-2.

Aim of the study: The aim of the present study was to investigate whether the FO influences growth and chemosensitivity of the colon cancer cell line Caco-2. FO was tested alone and in combination with the anticancer drug 5-fluorouracil (5-FU).

Methods: Cell numbers were determined with crystal violet staining, cell cycle distribution was assessed using a flow cytometer and apoptosis was visualized by staining nuclei with diamino-phenylindole hydrochloride.

Results: FO inhibited growth of Caco-2 cells in a time and dose dependent manner. FO treatment evoked apoptosis as confirmed by cell morphology. Cell cycle analysis identified an accumulation of cells in the G(2)/M phase after incubation with FO. The combined treatment of the cells with FO and 5-FU resulted in a significant enhancement of the growth inhibition seen after exposure to either substance alone. Treatment of the cells with 5-FU specifically blocked the cell cycle in the S phase. The combined treatment of 5-FU with FO showed a further increase in the accumulation of cells in the S phase.

Conclusions: In conclusion, FO has a potent antiproliferative effect on Caco-2 cells, at least in part, due to a decrease in the progression of the cell cycle and the induction of apoptosis. The combination of FO with 5-FU results in an additive growth inhibitory effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimetabolites, Antineoplastic / pharmacology*
  • Apoptosis / drug effects
  • Caco-2 Cells / cytology
  • Caco-2 Cells / drug effects*
  • Cell Cycle / drug effects
  • Cell Division / drug effects
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / pathology
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Fat Emulsions, Intravenous / chemistry
  • Fat Emulsions, Intravenous / pharmacology*
  • Fatty Acids, Omega-3 / pharmacology*
  • Flow Cytometry
  • Fluorouracil / pharmacology*
  • Humans
  • Tumor Cells, Cultured


  • Antimetabolites, Antineoplastic
  • Fat Emulsions, Intravenous
  • Fatty Acids, Omega-3
  • Fluorouracil