trans-10, cis-12 conjugated linoleic acid reduces insulin-like growth factor-II secretion in HT-29 human colon cancer cells.
We previously demonstrated that a mixture of conjugated linoleic acid (CLA) isomers decreases colon cancer incidence in rats treated with 1,2-dimethylhydrazine. Our in vitro studies have also shown that CLA inhibits the growth of HT-29 cells, a human colon cancer cell line. When we compared the individual potencies of the two main isomers found in the mixture of CLA isomers (e.g., cis-9, trans-11 [c9t11] and trans-10, cis-12 [t10c12]), t10c12 CLA decreased viable cell numbers in a dose-dependent manner. By contrast, c9t11 CLA had no effect. Therefore, the present study examined whether the decreased cell growth is related to changes in secretion of insulin-like growth factor (IGF)-II and/or IGF-binding proteins (IGFBPs) that have been shown to regulate HT-29 cell proliferation. Cells were incubated in serum-free medium with various concentrations of the individual CLA isomers, and immunoblot analysis of 24-hour, serum-free, conditioned media using a monoclonal anti-IGF-II antibody was performed. HT-29 cells secreted both mature 7,500 apparent molecular weight (M(r)) and higher-M(r) forms of IGF-II. t10c12 CLA decreased the levels of the higher-M(r) and the mature form of IGF-II in a dose-dependent manner, whereas c9t11 CLA had no effect. Ligand blot analysis of conditioned medium using (125)I-IGF-II revealed that the production of IGFBP-2 and IGFBP-4 was also decreased by t10c12 CLA, whereas c9t11 CLA had no effect. Exogenous IGF-II abrogated the growth inhibition induced by t10c12 CLA. These results indicate that inhibition of HT-29 cell growth by t10c12 CLA may be mediated by decreasing IGF-II secretion in these cells.
Division of Life Sciences and Silver Biotechnology Research Center, Hallym University, Chunchon, Korea.
Han Jin
HJ
Cho
Hyun Sook
HS
Lee
Cha-Kwon
CK
Chung
Young-Hee
YH
Kang
Yeong Lae
YL
Ha
Hyun-Suh
HS
Park
Jung Han Yoon
JH
Park
D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D019073:HT29 Cells; D006801:Humans; D015151:Immunoblotting; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D008970:Molecular Weight; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018969:Insulin-Like Growth Factor Binding Proteins; D044243:Linoleic Acids, Conjugated; D012333:RNA, Messenger; D007335:Insulin-Like Growth Factor II