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 (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.

• Authors: Eun J Kim, P Elly Holthuizen, Hyun S Park, Yeong L Ha, Kyeong C Jung, Jung H Y Park
• Journal: American journal of physiology. Gastrointestinal and liver physiology (Am J Physiol Gastrointest Liver Physiol) Vol. 283 Issue 2 Pg. G357-67 (Aug 2002) ISSN: 0193-1857 [Print] United States
• PMID: 12121883 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Messenger
• Insulin-Like Growth Factor II
• Linoleic Acid

Topics

• Apoptosis (drug effects)
• Caco-2 Cells
• Cell Division (drug effects, physiology)
• Colonic Neoplasms (pathology)
• Dose-Response Relationship, Drug
• Humans
• Insulin-Like Growth Factor II (antagonists & inhibitors, genetics, physiology)
• Linoleic Acid (administration & dosage, antagonists & inhibitors, pharmacology)
• RNA, Messenger (antagonists & inhibitors)