The relationship between growth and alterations in arachidonic acid (AA) metabolism in human breast (MCF-7) and colon (SW480) cancer cells was studied. Four different fatty acid preparations were evaluated: a mixture of conjugated linoleic acid (CLA) isomers (c9,t11, t10,c12, c11,t13, and minor amounts of other isomers), the pure c9,t11-CLA isomer, the pure t10,c12-CLA isomer, and linoleic acid (LA) (all at a lipid concentration of 16 microg/mL). 14C-AA uptake into the monoglyceride fraction of MCF-7 cells was significantly increased following 24 h incubation with the CLA mixture (P < 0.05) and c9,t11-CLA (P < 0.02). In contrast to the MCF-7 cells, 14C-AA uptake into the triglyceride fraction of the SW480 cells was increased while uptake into the phospholipids was reduced following treatment with the CLA mixture (P < 0.02) and c9,t11-CLA (P < 0.05). Distribution of 14C-AA among phospholipid classes was altered by CLA treatments in both cell lines. The c9,t11-CLA isomer decreased (P < 0.05) uptake of 14C-AA into phosphatidylcholine while increasing (P < 0.05) uptake into phosphatidylethanolamine in both cell lines. Both the CLA mixture and the t10,c12-CLA isomer increased (P < 0.01) uptake of 14C-AA into phosphatidylserine in the SW480 cells but had no effect on this phospholipid in the MCF-7 cells. Release of 14C-AA derivatives was not altered by CLA treatments but was increased (P < 0.05) by LA in the SW480 cell line. The CLA mixture of isomers and c9,t11-CLA isomer inhibited 14C-AA conversion to 14C-prostaglandin E2 (PGE2) by 20-30% (P < 0.05) while increasing 14C-PGF2alpha by 17-44% relative to controls in both cell lines. LA significantly (P < 0.05) increased 14C-PGD2 by 13-19% in both cell lines and increased 14C-PGE2 by 20% in the SW480 cell line only. LA significantly (P < 0.05) increased 5-hydroperoxyeicosatetraenoate by 27% in the MCF-7 cell line. Lipid peroxidation, as determined by increased levels of 8-epi-prostaglandin F2alpha (8-epi-PGF2alpha), was observed following treatment with c9,t11-CLA isomer in both cell lines (P < 0.02) and with t10,c12-CLA isomer in the MCF-7 cell line only (P < 0.05). These data indicate that the growth-promoting effects of LA in the SW480 cell line may be associated with enhanced conversion of AA to PGE2 but that the growth-suppressing effects of CLA isomers in both cell lines may be due to changes in AA distribution among cellular lipids and an altered prostaglandin profile.

The aims of this study were to determine whether vaccenic acid (VA; t11-18:1) is converted to c9,t11-CLA in human mammary (MCF-7) and colon (SW480) cancer cell lines and whether VA influences cell viability and other CLA-bioresponsive markers. When cells were incubated in the presence of VA at concentrations of 5 to 20 microg/mL, both VA and c9,t11-CLA increased in cellular lipids in a dose-dependent manner. After 4 d of incubation of SW480 and MCF-7 cells with VA (20 microg/mL), c9,t11-CLA increased from undetectable levels to 8.57 and 12.14 g/100 g FAME in cellular lipids, respectively. VA supplementation for 4 d at 5, 10, and 15 microg/mL had no effect on cell growth, whereas 20 microg/mL significantly (P < 0.05) reduced cell growth in both cell lines. VA (20 microg/mL) treatment induced DNA fragmentation and significantly (P < 0.05) depleted cytosolic GSH levels in the SW480 cell line after 4 d of incubation, suggesting that apoptosis was the mode of cell death induced by VA. Both VA and c9,t11-CLA reduced (P < 0.05) total ras expression in SW480 cells. 14C-Arachidonic acid uptake into the MG fraction was significantly increased (P < 0.05) in both cell lines while uptake into the phospholipid fraction decreased in response to VA. VA treatment significantly (P < 0.05) increased 8-epi-prostaglandin F2alpha in both cell lines. The data indicate that growth suppression and cellular responses of both cells lines are likely mediated by VA desaturation to c9,t11-CLA via delta9-desaturase.

Milk enriched in conjugated linoleic acid (CLA) was obtained from cows on pasture supplemented with full-fat rapeseeds (FFR; 2·26 g cis 9, trans 11 (c9, t11)-CLA/100 g fatty acid methyl esters) and full-fat soyabeans (1·83 g c9, t11-CLA/100 g fatty acid methyl esters). A control milk fat (1·69 g c9, t11-CLA/100 g fatty acid methyl esters) was obtained from cows fed on pasture only. The present study assessed the potency of the CLA-enriched milk fats to modulate biomarkers that had previously been observed to respond to c9, t11-CLA in the MCF-7 and SW480 cell lines. Cell numbers decreased (P,0·05) by up to 61 and 58 % following the incubation of MCF-7 and SW480 cells, respectively, for 4 d with milk fats (yielding CLA concentrations between 60·2 and 80·6 mM). The FFR milk fat, containing the highest CLA content, increased (P,0·05) [14 C]arachidonic acid (AA) uptake into the monoacylglycerol fraction of MCF-7 and SW480 cells while it decreased (P,0·05) uptake into the phospholipid fraction of the latter. This milk fat also decreased (P, 0·05) [14 C]AA conversion to prostaglandin (PG) E 2 while increasing conversion to PGF 2 a in both cell lines. All milk-fat samples increased (P, 0·05) lipid peroxidation as measured by 8-epi-PGF 2 a in both cell lines. In SW480 cells the milk-fat samples decreased (P, 0·05) bcl-2 and cytosolic glutathione levels while increasing (P, 0·05) membrane-associated annexin V levels. All milk-fat samples decreased (P,0·05) the expression of ras in SW480 cells. These data suggest that milk-fat CLA was effective at modulating synthetic CLA-responsive biomarkers.

Convincing evidence from rodent models of carcinogenesis indicates that cis-9,trans-11 (c9tll) conjugated linoleic acid (CLA) is a potent naturally occurring anti-carcinogen in the human diet. CLA has been reported to alter the fatty acid composition of biological tissues in a manner that increases their oxidative stability. However, recent information suggests that an antioxidant role for CLA does not seem plausible. Given the knowledge that c9tll CLA is present in a wide range of meat and dairy food products, our studies have begun to investigate mechanisms by which CLAenriched milk fat exerts its anti-carcinogenic effects. An oxidative mechanism appears to be involved in its growth-suppressive effects, since supplementation of growth culture medium with CLA (1 7-71.5 pM) made breast cancer cells more susceptible to lipid peroxidation. Studies have indicated that cancer cells may become enriched in CLA during growth in culture. This may make intracellular lipids more susceptible to ordinary

Convincing evidence from rodent models of carcinogenesis indicates that cis-9,trans-11 (c9t11) conjugated linoleic acid (CLA) is a potent naturally occurring anti-carcinogen in the human diet. CLA has been reported to alter the fatty acid composition of biological tissues in a manner that increases their oxidative stability. However, recent information suggests that an antioxidant role for CLA does not seem plausible. Given the knowledge that c9t11 CLA is present in a wide range of meat and dairy food products, our studies have begun to investigate mechanisms by which CLA-enriched milk fat exerts its anti-carcinogenic effects. An oxidative mechanism appears to be involved in its growth-suppressive effects, since supplementation of growth culture medium with CLA (17-71.5 microM) made breast cancer cells more susceptible to lipid peroxidation. Studies have indicated that cancer cells may become enriched in CLA during growth in culture. This may make intracellular lipids more susceptible to ordinary levels of oxidative stress, to the point of producing a cytotoxic effect.