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1 Division of Life Sciences and 5 Department of Pathology, Hallym University, Chunchon 200-702; 3 Department of Food and Nutrition, Kyung Hee University, Seoul 130-701; and 4 Division of Applied Life Sciences, Graduate School, Gyeongsang National University, Chinju 660-701, Korea; and 2 Laboratory for Physiological Chemistry, University Medical Center Utrecht, 3584 CG Utrecht, Netherlands
A commercially available mixture of conjugated linoleic acid (CLA) isomers decreases colon cancer cell growth. We compared the individual potencies of the two main isomers in this mixture [cis-9,trans-11 (c9t11) and trans-10,cis-12 (t10c12)] and assessed whether decreased cell growth is related to changes in secretion of insulin-like growth factor II (IGF-II) and/or IGF-binding proteins (IGFBPs), which regulate Caco-2 cell proliferation. Cells were incubated in serum-free medium with different concentrations of the individual CLA isomers. t10c12 CLA dose dependently decreased viable cell number (55 ± 3% reduction 96 h after adding 5 µM t10c12 CLA). t10c12 CLA induced apoptosis and decreased DNA synthesis, whereas c9t11 CLA had no effect. Immunoblot analysis of 24-h serum-free conditioned medium using a monoclonal anti-IGF-II antibody revealed that Caco-2 cells secreted both a mature 7,500 molecular weight (Mr) IGF-II and higher Mr forms of IGF-II. The levels of the higher Mr and the mature form of IGF-II were decreased 50 ± 3% and 22 ± 2%, respectively, by 5 µM t10c12 CLA. c9t11 CLA had no effect. Ligand blot analysis of conditioned medium using 125I-labeled IGF-II revealed that t10c12 CLA slightly decreased IGFBP-2 production; c9t11 CLA had no effect. Exogenous IGF-II reversed t10c12 CLA-induced growth inhibition and apoptosis. These results indicate that CLA-inhibited Caco-2 cell growth is caused by t10c12 CLA and may be mediated by decreasing IGF-II secretion in Caco-2 cells.
insulin-like growth factor binding proteins; apoptosis
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