Trans-10,cis-12, not cis-9,trans-11, conjugated linoleic acid inhibits G1-S progression in HT-29 human colon cancer cells

被引:49
|
作者
Cho, HJ
Kim, EJ
Lim, SS
Kim, MK
Sung, MK
Kim, JS
Park, JHY [1 ]
机构
[1] Hallym Univ, Dept Food Sci & Nutr, Chunchon 200702, South Korea
[2] Hallym Univ, Silver Biotechnol Res Ctr, Chunchon 200702, South Korea
[3] Natl Canc Ctr, Div Canc Control & Epidemiol, Goyang 411769, South Korea
[4] Sookmyung Womens Univ, Dept Food & Nutr, Seoul 140742, South Korea
[5] Kyungpook Natl Univ, Dept Anim Sci & Biotechnol, Taegu 702701, South Korea
来源
JOURNAL OF NUTRITION | 2006年 / 136卷 / 04期
关键词
conjugated linoleic acid; cell cycle; cyclin-dependent kinase; retinoblastoma protein; p21(CIP1/WAF1);
D O I
10.1093/jn/136.4.893
中图分类号
R15 [营养卫生、食品卫生]; TS201 [基础科学];
学科分类号
100403 ;
摘要
Commercial preparations of conjugated linoleic acid (CLA) contain both positional and geometric isomers of octadecadienoic acid, with cis-9,trans-11 CLA (c9t11) and trans-10,cis-12 CLA (t10c12) as the principal isomers. We showed previously that CLA reduced the incidence of colon tumors in rats treated with 1,2-dimethylhydrazine. In addition, our previous in vitro studies showed that t10c12 inhibited the growth of HT-29 and Caco-2 human colon cancer cells, whereas c9t11 had no effect on cell growth. In the present study, to examine the effects of the CLA isomers on cell cycle and cell cycle regulatory proteins, we treated HT-29 cells with various concentrations (0-4 mu mol/L) of the individual CLA isomers. A DNA flow cytometric analysis revealed that t10c12 induced a G, arrest, whereas c9t11 had no effect on the cell cycle. Western blot analysis of total cell lysates revealed no alteration in the protein expression of cyclin A, cyclin D, cyclin E, cyclin-dependent kinase (CDK) 2, or CDK4 due to t10c12 treatment. However, t10c12 substantially increased the protein expression and mRNA accumulation of the CDK inhibitor p21(CIP/WAF1). The t10c12 isomer increased the association of p21(CIP1/WAF1) with CDK2 and proliferating cell nuclear antigen, but decreased the levels of phosphorylated retinoblastoma protein (Rb), with an increase in the levels of hypophosphorylated Rb protein. An in vitro kinase assay using histone H1 as a substrate showed that the activities of CDK2 were significantly decreased by t10c12. These results indicate that t10c12 exerts its growth inhibitory effects in colon cancer cells through the induction of G, cell cycle arrest. The induction of p21(CIP1/WAF1) may be one of the mechanisms by which t10c12 inhibits cell cycle progression in HT-29 cells.
引用
收藏
页码:893 / 898
页数:6
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