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Logo of bmcgastBioMed Centralsearchsubmit a manuscriptregisterthis articleBMC Gastroenterology
 
BMC Gastroenterol. 2012; 12: 9.
Published online Jan 23, 2012. doi:  10.1186/1471-230X-12-9
PMCID: PMC3298530
Luteolin decreases IGF-II production and downregulates insulin-like growth factor-I receptor signaling in HT-29 human colon cancer cells
Do Young Lim,1 Han Jin Cho,1 Jongdai Kim,2,3 Chu Won Nho,4 Ki Won Lee,5 and Jung Han Yoon Parkcorresponding author1,2
1Department of Food Science and Nutrition, Hallym University, Chuncheon, 200-702, Korea
2Medical & Bio-Materials Research Center, Kangwon National University, Chuncheon, 200-701, Korea
3Department of Food Science and Biotechnology, Kangwon National University, Chuncheon, 200-701, Korea
4Functional Food Center, Korea Institute of Science and Technology, Gangneung Institute, Gangneung, 210-340, Korea
5Department of Agricultural Biotechnology and Center for Agricultural Biomaterials, Seoul National University, Seoul, 151-921, Korea
corresponding authorCorresponding author.
Do Young Lim: ldydo/at/daum.net; Han Jin Cho: hanjini/at/hallym.ac.kr; Jongdai Kim: jongdai/at/kangwon.ac.kr; Chu Won Nho: cwnho/at/kist.re.kr; Ki Won Lee: kiwon/at/snu.ac.kr; Jung Han Yoon Park: jyoon/at/hallym.ac.kr
Received June 24, 2011; Accepted January 23, 2012.
Abstract
Background
Luteolin is a 3',4',5,7-tetrahydroxyflavone found in various fruits and vegetables. We have shown previously that luteolin reduces HT-29 cell growth by inducing apoptosis and cell cycle arrest. The objective of this study was to examine whether luteolin downregulates the insulin-like growth factor-I receptor (IGF-IR) signaling pathway in HT-29 cells.
Methods
In order to assess the effects of luteolin and/or IGF-I on the IGF-IR signaling pathway, cells were cultured with or without 60 μmol/L luteolin and/or 10 nmol/L IGF-I. Cell proliferation, DNA synthesis, and IGF-IR mRNA levels were evaluated by a cell viability assay, [3H]thymidine incorporation assays, and real-time polymerase chain reaction, respectively. Western blot analyses, immunoprecipitation, and in vitro kinase assays were conducted to evaluate the secretion of IGF-II, the protein expression and activation of IGF-IR, and the association of the p85 subunit of phophatidylinositol-3 kinase (PI3K) with IGF-IR, the phosphorylation of Akt and extracellular signal-regulated kinase (ERK)1/2, and cell division cycle 25c (CDC25c), and PI3K activity.
Results
Luteolin (0 - 60 μmol/L) dose-dependently reduced the IGF-II secretion of HT-29 cells. IGF-I stimulated HT-29 cell growth but did not abrogate luteolin-induced growth inhibition. Luteolin reduced the levels of the IGF-IR precursor protein and IGF-IR transcripts. Luteolin reduced the IGF-I-induced tyrosine phosphorylation of IGF-IR and the association of p85 with IGF-IR. Additionally, luteolin inhibited the activity of PI3K activity as well as the phosphorylation of Akt, ERK1/2, and CDC25c in the presence and absence of IGF-I stimulation.
Conclusions
The present results demonstrate that luteolin downregulates the activation of the PI3K/Akt and ERK1/2 pathways via a reduction in IGF-IR signaling in HT-29 cells; this may be one of the mechanisms responsible for the observed luteolin-induced apoptosis and cell cycle arrest.
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