2012年1月22日,，據(jù)《每日科學(xué)》報(bào)道,，木犀草素，一種常見(jiàn)于水果和蔬菜中的黃酮類(lèi)化合物,。在實(shí)驗(yàn)室條件下,，這種化合物被證明具有抗炎、抗氧化和抗癌特性,，但來(lái)自流行病學(xué)研究的結(jié)果不那么確定,。發(fā)表于BMC Gastroenterology上的一項(xiàng)新研究表明，木犀草素能夠抑制結(jié)腸癌細(xì)胞中對(duì)于癌癥生長(zhǎng)非常重要的細(xì)胞信號(hào)通路（IGF和PI3K）,。
結(jié)腸癌是西方國(guó)家第二大常見(jiàn)癌癥相關(guān)死亡的原因,。與正常的結(jié)腸組織相比，結(jié)腸癌細(xì)胞中的IGF-II水平升高,。據(jù)認(rèn)為,，這是驅(qū)動(dòng)細(xì)胞不受控制的分裂及癌癥生長(zhǎng)的機(jī)制的一部分。來(lái)自韓國(guó)的研究人員發(fā)現(xiàn),，木犀草素能夠阻止結(jié)腸癌細(xì)胞分泌IGF-II并在2小時(shí)內(nèi)降低受體（IGF-IR）前體蛋白的總量,。木犀草素也減少了活性受體的總量（通過(guò)IGF-I依賴(lài)的磷酸化測(cè)量）。
木犀草素抑制了IGF-I的生長(zhǎng)刺激作用,，由Jung Han Yoon Park教授領(lǐng)導(dǎo)的小組發(fā)現(xiàn),，木犀草素影響了在癌癥中由IGF-I激活的細(xì)胞信號(hào)通路。Jung Han Yoon Park教授解釋說(shuō),，木犀草素降低了PI3K,、Akt、ERK1/2和CDC25c細(xì)胞信號(hào)通路中IGF-I依賴(lài)的激活,。阻斷這些通路能阻止癌細(xì)胞的分裂并導(dǎo)致癌細(xì)胞死亡,。
Jung Park教授繼續(xù)說(shuō)，"我們的研究表明,，木犀草素干擾了結(jié)腸癌細(xì)胞中的細(xì)胞信號(hào),，這為了解這種黃酮物質(zhì)如何作用邁出了一步。更全面的了解體內(nèi)研究結(jié)果對(duì)于確定它如何可能被開(kāi)發(fā)成一種有效的化學(xué)預(yù)防劑至關(guān)重要,。"（生物谷bioon.com）
doi:10.1186/1471-230x-12-9
PMC:
PMID:
Luteolin decreases IGF-II production and downregulates insulin-like growth factor-I receptor signaling in HT-29 human colon cancer cells
Do Young Lim, Han Jin Cho, Jongdai Kim, Chu Won Nho, Ki Won Lee and Jung Han Yoon Park
Abstract (provisional)： 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 micromol/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 micromol/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.
