[show abstract][hide abstract] ABSTRACT: Conjugated linoleic acid (CLA) consists of a group of naturally occurring and synthetic positional and geomet-ric (cis-trans) stereoisomers of the polyunsaturated fatty acid linoleic acid. The cis-9,trans-11 (c9,t11) CLA isomer (the most prevalent form found in ruminant-derived foods) and the trans-10,cis-12 (t10,c12) CLA isomer (present in commer-cial preparations) are the two most widely studied CLA isomers in breast cancer. Studies using both animal and cell cul-ture models indicate that these CLA isomers, when added to the diet or included in the cell culture medium, inhibit mam-mary tumour initiation, promotion and progression in rodents, and alter tumour cell viability in vitro. The mechanism of CLA's anticancer effect is not well understood, but may involve interference with the cell cycle, induction of apoptosis, modulation of gene expression via the activation of peroxisome proliferator-activated receptors, lipid peroxidation, modu-lation of the tumour microenvironment, changes to the structure and/or function of the cell membrane, and interference with growth factor receptor signaling. A greater understanding of the mechanism of action of CLA will support the devel-opment of clinical trials to evaluate the potential effectiveness of CLA in the treatment of breast cancer.
[show abstract][hide abstract] ABSTRACT: In vitro work suggests that conjugated linoleic acid (CLA) isomers (c9,t11 and t10,c12) are cytotoxic to human breast cancer cells, however the mechanism remains unknown. Using human MCF-7 breast cancer cells, we examined the effects of c9,t11 and t10,c12 CLA compared to oleic acid (OA), linoleic acid (LA), or untreated cells on cell membrane phospholipid composition, cell survival, and the insulin-like growth factor-I (IGF-I) and the downstream insulin receptor substrate-1 (IRS-1). Both CLA isomers were incorporated into membrane phospholipids (p < 0.05). Compared to untreated cells, c9,t11 or t10,c12 CLA significantly reduced the metabolic activity of IGF-I stimulated MCF-7 cells, increased lactate dehydrogenase (LDH) release, and decreased cellular concentrations of the IGF-I receptor (IGF-IR) and insulin receptor substrate-1 (p < 0.05). Incubation with t10,c12 CLA also reduced the levels of phosphorylated IGF-1R. The effects on all of these measures were greater (p < 0.05) for t10,c12 CLA compared to c9,t11 CLA. There were few differences between LA-treated and c9,t11 CLA-treated cells, whereas cellular metabolic activity, LDH release, and IGF-IR concentrations differed between t10,c12 CLA-treated and LA-treated cells (p < 0.05). OA stimulated growth compared to the untreated condition (p < 0.05). In summary, this study demonstrated that the t10,c12 CLA isomer inhibits growth of MCF-7 cells and suggested that this may be mediated through incorporation into cellular phospholipids and interference with the function of IGF-I and related signaling proteins.