Trans-10,cis-12-conjugated linoleic acid inhibits Caco-2 colon cancer cell growth

Abstract

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 ( c9 t11) and trans-10, cis-12 ( t10 c12)] 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. t10 c12 CLA dose dependently decreased viable cell number (55 ± 3% reduction 96 h after adding 5 μM t10 c12 CLA). t10 c12 CLA induced apoptosis and decreased DNA synthesis, whereas c9 t11 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 ( M r) IGF-II and higher M r forms of IGF-II. The levels of the higher M r and the mature form of IGF-II were decreased 50 ± 3% and 22 ± 2%, respectively, by 5 μM t10 c12 CLA. c9 t11 CLA had no effect. Ligand blot analysis of conditioned medium using125I-labeled IGF-II revealed that t10 c12 CLA slightly decreased IGFBP-2 production; c9 t11 CLA had no effect. Exogenous IGF-II reversed t10 c12 CLA-induced growth inhibition and apoptosis. These results indicate that CLA-inhibited Caco-2 cell growth is caused by t10 c12 CLA and may be mediated by decreasing IGF-II secretion in Caco-2 cells.