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.
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.


OBJECTIVE
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.
Jordan
Angela
A
2nd Dept. of Medicine, Johann Wolfgang Goethe University, Theodor Stern Kai 7, 60590, Frankfurt, Germany.
Stein
Jürgen
J
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D018938:Caco-2 Cells / Q000166:cytology / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005217:Fat Emulsions, Intravenous / Q000737:chemistry / Q000494:pharmacology*; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005434:Flow Cytometry; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D005217:Fat Emulsions, Intravenous; D015525:Fatty Acids, Omega-3; D005472:Fluorouracil