An Enriched Mixture of Trans-10,Cis-12-CLA Inhibits Linoleic Acid Metabolism and PGE2 Synthesis in MDA-MB-231 Cells

Abstract

Abstract: Conjugated linoleic acid (CLA) isomers are potent inhibitors of mammary tumor cell growth. Evidence suggests that CLA modulates essential fatty acid (EFA) metabolism; however, it is not clear which parts of this pathway are important regulatory points modulated by CLA. Enriched mixtures of D9-cis,11-trans (D9c,11t)- and D10-trans,12-cis (D10t,12c)-18:2 were used to assess outcome measures of EFA metabolism pertaining to membrane phospholipid incorporation, tumor cell growth, and prostaglandin E2 (PGE2) synthesis in the MDA-MB-231 mammary tumor cell line. Tumor cells were treated with linoleic acid (LA), an equal mixture (Mix), or enriched preparations of D9c,11t- or D10t,12c-18:2. Treatment with Mix or the enriched mixture of D10t,12c-18:2 significantly inhibited the synthesis of arachidonic acid (AA) from LA, resulting in increased levels of LA and decreased levels of AA in membrane phosphatidylcholine and phosphatidylethanolamine (P < 0.05). LA and AA levels were not altered in cells treated with enriched D9c,11t-18:2 and were similar to those in LA control treated cells. All CLA treatments reduced [3H]thymidine uptake, an indicator of tumor cell growth, by more than one-half relative to LA controls. MDA-MB-231 cells challenged with AA in the presence of all CLA mixtures resulted in significantly reduced PGE2 synthesis relative to controls treated with LA (P < 0.05). It is evident that individual isomers exert inhibitory effects at specific steps of EFA metabolism, which correspondingly leads to a reduction in PGE2 synthesis and, ultimately, tumor growth.