Comparison of linoleic acid and eicosapentaenoic acid incorporation into human breast cancer cells

Abstract

To gain some insight into the mechanisms involved in the opposing effects of linoleic acid (LA) and eicosapentaenoic acid (EPA) on the growth and invasiveness of MDA-MB-435 human breast cancer cells, the dynamics of the uptake by cells and the incorporation of [14C]LA and [14C]EPA into major lipid and phospholipid pools, as well as the effects of unlabeled EPA or LA on the uptake and distribution of [14C]LA or [14C]EPA, respectively, were examined. Cells were exposed to [14C]LA (1.28 micrograms/mL) or [14C]EPA (1.0 micrograms/mL) and unlabeled EPA or LA, respectively, at 0, 1, 4 and 16 micrograms/mL for 24 h in serum-free media. The uptake of each fatty acid (FA) was linear over time and was not affected by the presence of the opposing FA. For both FA, 80-90% was incorporated into the phospholipid fraction with the remaining 10-20% in neutral lipids. The relative distribution profile of [14C]LA among the phospholipid classes indicated a preferential incorporation into phosphatidylcholine (65%), whereas [14C]EPA was mostly found in phosphatidylethanolamine (58%). In the presence of unlabeled EPA or LA at various concentrations, corresponding dose-dependent shifts of [14C]LA or [14C]EPA from the phospholipid to the neutral lipid pool were noted, which did not alter the relative distribution of the FA among the phospholipid classes. Exogenous exposure to EPA or LA increased its content in membrane phospholipids while concurrently decreasing LA or EPA content, respectively, in a dose-dependent manner. Arachidonic acid content of membrane phospholipids remained constant.(ABSTRACT TRUNCATED AT 250 WORDS)

Omega‐3 polyunsaturated fatty acids attenuate breast cancer growth through activation of a neutral sphingomyelinase‐mediated pathway

“…[1][2][3][4] The anticancer role of omega-3 fatty acids has also been substantiated with dietary studies using many types of animals (including humans) and numerous different cell lines, including breast cancer. 8,10,19,20 In the study reported here, we investigated the effects of long-chain polyunsaturated omega-3 fatty acids on breast cancer cells both in vivo and in vitro.…”

“…Numerous studies, including our own, 5,[19][20][21][22][23][24] have linked fish oil to induction of apoptosis. We found that DHA activates sphingomyelinase (SMYase) activity in the plasma membrane of Jurkat leukemic cells, increasing ceramide levels.…”

Differential effects of prostaglandin derived from ω-6 and ω-3 polyunsaturated fatty acids on COX-2 expression and IL-6 secretion

“…It has been shown that both -3 and -6 long-chain PUFA added exogenously to cells in culture become part of the membrane phospholipid pool (24,25). Accumulation of exogenously added PUFA occurs in the phospholipid component of the membranes during the first 8-16 h of exposure, after which there was little or no accumulation.…”

Docosahexaenoic acid affects cell signaling by altering lipid rafts

“…The preponderence of reports coming from a vide variety of primarily cancer cell types [155][156][157][158][159] indicate that DHA induces apoptosis and it has been suggested that DHA's anticancer properties are not due directly to cytotoxicity, but rather to the fatty acid's ability to induce apoptosis [160][161][162]. Siddiqui et al [163] have recently reviewed the role of DHA in enhancing both the cytosol-linked and mitochondrial-linked apoptotic pathways.…”