QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kim, E. J. Articles by Park, J. H. Y. Search for Related Content PubMed PubMed Citation Articles by Kim, E. J. Articles by Park, J. H. Y.

---

Nutrition and Cancer

Conjugated Linoleic Acid Downregulates Insulin-Like Growth Factor-I Receptor Levels in HT-29 Human Colon Cancer Cells

Eun Ji Kim^*, Il-Jun Kang^*, Han Jin Cho^*, Woo Kyoung Kim^**, Yeong-Lae Ha and Jung Han Yoon Park^*,2

^* Division of Life Sciences and Silver Biotechnology Research Center, Hallym University, Chunchon, 200–702, Korea, ^** Department of Food Science and Nutrition, Dankook University, Seoul, 140–714, Korea, and Division of Applied Life Sciences, Graduate School, Gyeongsang National University, Chinju, 660–901, Korea

²To whom correspondence should be addressed. E-mail: jyoon{at}hallym.ac.kr.

Conjugated linoleic acid (CLA) has chemoprotective properties in a variety of experimental cancer models. We have previously observed that dietary CLA inhibits colon tumorigenesis induced by 1,2-dimethylhydrazine in rats. In addition, our in vitro studies have shown that CLA inhibits DNA synthesis and induces apoptosis in HT-29 cells, the human colon adenocarcinoma cell line. The insulin-like growth factor (IGF) system regulates the growth of HT-29 cells by an autocrine mechanism. The present study examined whether the growth inhibitory effect of CLA is related to changes in the IGF system in HT-29 cells. To determine whether CLA inhibits IGF-II production, HT-29 cells were incubated in serum-free medium in the presence of various concentrations of CLA. CLA decreased protein levels of both mature and pro IGF-II and IGF-II transcripts. Whereas exogenous IGF-I and IGF-II produced an increase in cell number, neither IGF-I nor IGF-II counteracted the negative growth regulatory effect of CLA. Reverse transcriptase-polymerase chain reaction and Western blot analysis of total cell lysates revealed that CLA decreased IGF-I receptor (IGF-IR) transcript and protein levels in a dose-dependent manner. Immunoprecipitation/Western blot studies revealed that CLA inhibited IGF-I–induced phosphorylation of IGF-IR and insulin-receptor substrate (IRS)-1, recruitment of the p85 regulatory subunit of phosphatidylinositol 3-kinase (PI3K) to IGF-IR, IGF-IR–associated PI3K activity, and phosphorylated Akt and extracellular signal-regulated kinase (ERK)-1/2 levels. In conclusion, the inhibition of cell proliferation and induction of apoptosis by CLA in HT-29 cells may be mediated in part by its ability to decrease IGF-II synthesis and to downregulate IGF-IR signaling and the PI3K/Akt and ERK-1/2 pathways.

KEY WORDS: • insulin-receptor substrate-1 • Akt • extracellular signal-regulated kinase

This article has been cited by other articles:

				X. Meng, S. F. Shoemaker, S. O. McGee, and M. M. Ip t10,c12-Conjugated linoleic acid stimulates mammary tumor progression in Her2/ErbB2 mice through activation of both proliferative and survival pathways Carcinogenesis, May 1, 2008; 29(5): 1013 - 1021. [Abstract] [Full Text] [PDF]

				D. Y. Lim, Y. Jeong, A. L. Tyner, and J. H. Y. Park Induction of cell cycle arrest and apoptosis in HT-29 human colon cancer cells by the dietary compound luteolin Am J Physiol Gastrointest Liver Physiol, January 1, 2007; 292(1): G66 - G75. [Abstract] [Full Text] [PDF]

				S.-H. Lee, K. Yamaguchi, J.-S. Kim, T. E. Eling, S. Safe, Y. Park, and S. J. Baek Conjugated linoleic acid stimulates an anti-tumorigenic protein NAG-1 in an isomer specific manner Carcinogenesis, May 1, 2006; 27(5): 972 - 981. [Abstract] [Full Text] [PDF]

				H. J. Cho, E. J. Kim, S. S. Lim, M. K. Kim, M.-K. Sung, J.-S. Kim, and J. H. Y. Park Trans-10,cis-12, Not cis-9,trans-11, Conjugated Linoleic Acid Inhibits G1-S Progression in HT-29 Human Colon Cancer Cells J. Nutr., April 1, 2006; 136(4): 893 - 898. [Abstract] [Full Text] [PDF]

				S. C. Degner, M. Q. Kemp, G. T. Bowden, and D. F. Romagnolo Conjugated Linoleic Acid Attenuates Cyclooxygenase-2 Transcriptional Activity via an Anti-AP-1 Mechanism in MCF-7 Breast Cancer Cells J. Nutr., February 1, 2006; 136(2): 421 - 427. [Abstract] [Full Text] [PDF]

				X. Lu, J. i. Jung, H. J. Cho, D. Y. Lim, H. S. Lee, H. S. Chun, D. Y. Kwon, and J. H. Park Fisetin Inhibits the Activities of Cyclin-Dependent Kinases Leading to Cell Cycle Arrest in HT-29 Human Colon Cancer Cells J. Nutr., December 1, 2005; 135(12): 2884 - 2890. [Abstract] [Full Text] [PDF]