Trans-10,cis-12-conjugated linoleic acid inhibits Caco-2 colon cancer cell growth.
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 microM 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 (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 microM 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.
Kim
Eun J
EJ
Division of Life Sciences, Hallym University, Chunchon 200-702, Korea.
Holthuizen
P Elly
PE
Park
Hyun S
HS
Ha
Yeong L
YL
Jung
Kyeong C
KC
Park
Jung H Y
JH
D017209:Apoptosis / Q000187:drug effects; D018938:Caco-2 Cells; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D003110:Colonic Neoplasms / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D019787:Linoleic Acid / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors
D012333:RNA, Messenger; D007335:Insulin-Like Growth Factor II; D019787:Linoleic Acid