Effect of eicosapentaenoic acid and other fatty acids on the growth in vitro of human pancreatic cancer cell lines.
A number of polyunsaturated fatty acids have been shown to inhibit the growth of malignant cells in vitro. To investigate whether fatty acids modify the growth of human pancreatic cancer, lauric, stearic, palmitic, oleic, linoleic, alpha-linolenic, gamma-linolenic, arachidonic, docosahexaenoic and eicosapentaenoic (EPA) acids were each incubated with the cells lines MIA PaCa-2, PANC-1 and CFPAC at concentrations ranging from 1.25 microM to 50 microM and the effect of each fatty acid on cell growth was examined. All the polyunsaturated fatty acids tested had an inhibitory effect, with EPA being the most potent (ID50 2.5-5 microM). Monounsaturated or saturated fatty acids were not inhibitory. The action of EPA could be reversed with the anti-oxidant vitamin E acetate or with oleic acid. The cyclo-oxygenase inhibitors indomethacin and piroxicam had no effect on the action of EPA. The action of EPA appeared to be associated with the generation of lipid peroxides, although the level of lipid peroxidation did not always appear to correlate directly with the extent of cell death. The ability of certain fatty acids to inhibit significantly the growth of three human pancreatic cancer cell lines in vitro at concentrations which could be achieved in vivo suggests that administration of such fatty acids may be of therapeutic benefit in patients with pancreatic cancer.
Falconer
J S
JS
University Department of Surgery, Royal Infirmary, Edinburgh, UK.
Ross
J A
JA
Fearon
K C
KC
Hawkins
R A
RA
O'Riordain
M G
MG
Carter
D C
DC
D002455:Cell Division / Q000187:drug effects; D003470:Culture Media / Q000737:chemistry; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects*; D010190:Pancreatic Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured
D003470:Culture Media; D005231:Fatty Acids, Unsaturated; D015118:Eicosapentaenoic Acid