An enriched mixture of trans-10,cis-12-CLA inhibits linoleic acid metabolism and PGE2 synthesis in MDA-MB-231 cells.
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.
Nutrition and Metabolism Research Group and the Department of Medicine, University of Alberta, Edmonton, AB, Canada T6G 2P5.
David W L
DW
Ma
Catherine J
CJ
Field
Michael T
MT
Clandinin
D000704:Analysis of Variance; D016718:Arachidonic Acid / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism*; D015232:Dinoprostone / Q000096:biosynthesis*; D005260:Female; D020404:Glycerophospholipids / Q000378:metabolism; D006801:Humans; D019787:Linoleic Acid / Q000378:metabolism* / Q000494:pharmacology*; D008041:Linoleic Acids / Q000494:pharmacology*; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D013237:Stereoisomerism; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000378:metabolism
C094849:10,12-octadecadienoic acid; D020404:Glycerophospholipids; D008041:Linoleic Acids; D044243:Linoleic Acids, Conjugated; C046938:9,11-linoleic acid; D016718:Arachidonic Acid; D019787:Linoleic Acid; D015232:Dinoprostone