Trans-10,cis-12, not cis-9,trans-11, conjugated linoleic acid decreases ErbB3 expression in HT-29 human colon cancer cells.
OBJECTIVE
To examine whether trans-10,cis-12 CLA (t10c12) or cis-9,trans-11 CLA (c9t11) inhibits heregulin (HRG)-beta-stimulated cell growth and HRG-beta-ErbB3 signaling in HT-29 cells.


METHODS
We cultured HT-29 cells in the absence or presence of the CLA isomers and/or the ErbB3 ligand HRG-beta. MTT assay, [3H]thymidine incorporation, Annexin V staining, RT-PCR, Western blotting, immunoprecipitation, and in vitro kinase assay were performed.


RESULTS
HRG-beta increased cell growth, but did not prevent t10c12-induced growth inhibition. T10c12 inhibited DNA synthesis and induced apoptosis of HT-29 cells, whereas c9t11 had no effect. T10c12 decreased the levels of ErbB1, ErbB2, and ErbB3 proteins and transcripts in a dose-dependent manner, whereas c9t11 had no effect. Immunoprecipitation/Western blot studies revealed that t10c12 inhibited HRG-beta-stimulated phosphorylation of ErbB3, recruitment of the p85 subunit of phosphoinositide 3-kinase (PI3K) to ErbB3, ErbB3-associated PI3K activities, and phosphorylation of Akt. However, c9t11 had no effect on phospho Akt levels. Neither t10c12 nor c9t11 had any effect on HRG-beta-induced phosphorylation of ERK-1/2.


CONCLUSIONS
These results indicate that the inhibition of HT-29 cell growth by t10c12 may be induced via its modulation of ErbB3 signaling leading to inhibition of Akt activation.
Cho
Han Jin
HJ
Department of Food Science and Nutrition, Hallym University, 1 Okchon Dong, Chuncheon 200-702, Korea.
Kim
Woo Kyoung
WK
Jung
Jae In
JI
Kim
Eun Ji
EJ
Lim
Soon Sung
SS
Kwon
Dae Young
DY
Park
Jung Han Yoon
JH
D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D019073:HT29 Cells; D006801:Humans; D044243:Linoleic Acids, Conjugated / Q000737:chemistry* / Q000494:pharmacology*; D020893:Receptor, ErbB-3 / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism
D044243:Linoleic Acids, Conjugated; D020893:Receptor, ErbB-3