Effect of eicosapentaenoic acid and other fatty acids on the growth in vitro of human pancreatic cancer cell lines

Abstract

Summary 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 JAM to 5011M 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 gM).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.

Cell cycle arrest and induction of apoptosis in pancreatic cancer cells exposed to eicosapentaenoic acid in vitro

“…EPA has previously been shown to inhibit the growth of pancreactic cancer cell lines (Falconer et al, 1994). In the current study, we have observed similar inhibitory effects with EPA supplementation.…”

“…In addition, the effects of indomethacin on various in vitro models show that it can either stimulate or inhibit tumour cell proliferation (Buckman et al, 1991;Fulton, 1984;Rose and Connolly, 1990;Bayer et al, 1979;Hial et al, 1977). Other studies have suggested that increased lipid peroxidation may be an important cause of cytotoxicity associated with n-3 PUFAs but a definite role has not been established (Falconer et al, 1994;Lystad et al, 1994).…”

“…We have previously examined the action of a variety of fatty acids on the growth of three human pancreatic cancer cell lines (MIA PaCa-2, PANC-1 and CFPAC). These studies demonstrated that, at concentrations of fatty acids ranging from 5 to 50 ,uM, EPA was one of the most effective inhibitors of cell growth (Falconer et al, 1994). Studies with mice bearing the MAC-16 colon adenocarcinoma have demonstrated a marked inhibition of both tumour growth rate and associated cachexia following dietary supplementation with EPA Tisdale and Dhesi, 1990).…”

“…Fatty acids were complexed to BSA according to the method described previously (Falconer et al, 1994) (Falconer et al, 1994) to have no effect on the growth of pancreatic cancer cell lines, was chosen as a control fatty acid. BSA was also used as another control as both PA and EPA used in the experiments were albumin complexed.…”

Specific fatty acid intake and the risk of pancreatic cancer in Canada

“…Experimental studies of pancreatic cancer indicate that while dietary fat per se does not cause pancreatic cancer (Roebuck, 1992), individual polyunsaturated fatty acids (FAs), but not monounsaturated or saturated FAs, have an inhibitory effect on the growth of human pancreatic cancer cell lines (Falconer et al, 1994), suggesting that an association between dietary fats and pancreatic cancer may depend on the level of specific FA intake.…”