Trans-10, cis-12, not cis-9,trans-11, conjugated linoleic acid decreases ErbB3 expression in HT-29 human colon cancer cells

• Published in: World journal of gastroenterology : WJG Vol. 11; no. 33; pp. 5142 - 5150
• Main Authors: Cho, Han Jin, Kim, Woo Kyoung, Jung, Jae In, Kim, Eun Ji, Lim, Soon Sung, Kwon, Dae Young, Park, Jung Han Yoon
• Format: Journal Article
• Language: English
• Published: United States Baishideng Publishing Group Inc 07.09.2005
• Subjects: Cell Division - drug effects; cis-12共轭亚麻酸; cis-9,trans-11共轭亚麻酸; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; Colorectal Cancer; ErbB3; HT29 Cells; Humans; Linoleic Acids, Conjugated - chemistry; Linoleic Acids, Conjugated - pharmacology; Receptor, ErbB-3 - antagonists & inhibitors; Stereoisomerism; Trans-10; 基因表达; 结肠癌
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v11.i33.5142

AIM： To examine whether trans-10,cis-12 CLA （t10C12） or cis-9,trans-11 CLA （c9t11） inhibits heregulin （HRG）-β- stimulated cell growth and HRG-β-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-β. MTT assay, [^3H]thymidine incorporation, Annexin V staining, RT-PCR, Western blotting, immunoprecipitation, and in vitro kinase assay were performed. RESULTS： HRG-β increased cell growth, but did not prevent DNA 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- β-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 Aid： levels. Neither t10c12 nor c9t11 had any effect on HRG-β-induced phosphorylation of ERK-1/2. CONCLUSION： 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.