Modulation of arachidonic acid distribution by conjugated linoleic acid isomers and linoleic acid in MCF‐7 and SW480 cancer cells

Abstract

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.

Effects of cis-9, trans-11 and trans-10, cis-12 conjugated linoleic acid (CLA) isomers on immune function in healthy men

“…However, the data on effects of CLA on PGE 2 production seem inconsistent, as several studies have shown inhibition of PGE 2 production in vitro (Liu & Belury, 1998;Miller et al, 2001) and in CLA-supplemented rats Sugano et al, 1997Sugano et al, , 1998 and guinea pigs (Whigham et al, 2001(Whigham et al, , 2002. Other studies are in line with our current finding as they found no significant reduction of PGE 2 production in humans (Kelley et al, 2001), mice (Hayek et al, 1999) and rats (Turek et al, 1998).…”

Conjugated linoleic acid suppresses colon carcinogenesis in azoxymethane-pretreated rats with long-term feeding of diet containing beef tallow

“…Several studies of cancer cell lines from various organs have shown a difference between t10, c12-CLA and c9, t11-CLA. Namely, the suppressive effect of CLA on COX-2 expression is affected by c9, t11-CLA, and an alternative mechanism is induced by t10, c12-CLA [44][45][46]. In our present study, supplementation with CLA-FFA and CLA-TG inhibited the expression of COX-2, PGE2, and TXB2 in the colon mucosa.…”

“…*p \ 0.05 compared with azoxymethane (AOM)-pretreated rats fed with 10% beef tallow only; **p \ 0.05 compared with saline-pretreated rats fed with 10% beef tallow only; and p \ 0.05 compared with AOM-pretreated rats in each dietary group. BT, Beef tallow alone; TG, BT and 1% conjugated linoleic acid triglyceride form; FFA, BT and 1% conjugated linoleic acid free fatty acid form J Gastroenterol (2010) 45:625-635 633 arachidonic acid distribution among cellular lipids, and an altered prostaglandin profile [46]. Several studies of cancer cell lines from various organs have shown a difference between t10, c12-CLA and c9, t11-CLA.…”

The Role of Conjugated Linoleic Acid in Breast Cancer Growth and Development

“…Phospholipase A2 preferentially detaches fatty acids from phosphatidylcholine (PC), making PC the preferential source of AA for eicosanoid synthesis. Miller et al [94] showed that CLA decreases the amount of AA stored in PC and increases it in phosphatidylethanolamine (PE) along with a subsequent decrease in the production of PGE 2. Although these researchers have reported that CLA may interfere with essential fatty acid metabolism, the more effective isomer is still controversial [92,94].…”