Article

Luteolin inhibits invasion of prostate cancer PC3 cells through E-cadherin

Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, SIBS, Chinese Academy of Sciences, Shanghai.
Molecular Cancer Therapeutics (Impact Factor: 6.11). 07/2009; 8(6):1684-91. DOI: 10.1158/1535-7163.MCT-09-0191
Source: PubMed

ABSTRACT Luteolin, a common dietary flavonoid, has been found to have antitumor properties and therefore poses special interest for the development of preventive and/or therapeutic agent for cancers. E-cadherin, a marker of epithelial cells, mediates cell-cell adhesion. Decreased expression of E-cadherin results in a loss of cell-cell adhesion and an increased cell invasion. Many studies have shown the antiproliferative activities of luteolin on cancer cells. However, the effects of luteolin on invasion of cancer cells remain unclear. In this article, we show that luteolin inhibits invasion of prostate cancer PC3 cells through E-cadherin. We found that Luteolin induced expression of E-cadherin through mdm2. Overexpression of mdm2 or knockdown of E-cadherin could restore invasion of PC3 cells after luteolin treatment. Luteolin inhibits mdm2 through AKT and overexpression of active AKT attenuated luteolin-induced expression of E-cadherin, suggesting that luteolin regulates E-cadherin through AKT/mdm2 pathway. The in vivo experiments showed that luteolin inhibited spontaneous lung metastasis of PC3 cells implanted onto the nude mice. These findings provide a new sight into the mechanisms that luteolin is against cancer cells, and suggest that molecular targeting of E-cadherin by luteolin may be a useful strategy for treatment of invasive prostate cancers.

0 Followers
 · 
94 Views
  • Source
    • "The pursuit of novel compounds able to block or reverse EMT has become an emerging issue. Luteolin, a well-known flavonoid compound, has been reported to inhibit the migration/invasion and prevent the EMT phenomenon of some malignant cancers such as PC-3 (prostate cancer) and A431 (skin cancer) (Lee et al., 2006; Zhou et al., 2009). Other flavonoid compounds including quercetin, epigallocatechin-3-gallate, apigenin, theaflavin, and baicalein exhibit similar inhibitory effects of migration/invasion and EMT in skin, melanoma, breast, and HCC (hepatocellularcarcinoma) cells (Noh et al., 2010; Sil et al., 2010; Wang et al., 2010). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Luteolin is a natural flavonoid that possesses a variety of pharmacological activities, such as anti-inflammatory and anti-cancer abilities. Whether luteolin regulates the transformation ability of Lung cancer cells remains unclear. The current study aims to uncover the effects and underling mechanisms of luteolin in regulation of and Epithelial-mesenchymal transition of lung cancer cells. The lung adenocarcinoma A549 cells were used in this experiment; the cells were pretreated with luteolin followed by administration with TGF-β1. The expression levels of various cadherin and related upstream regulatory modules were examined, KEY FINDINGS: Pretreatment of luteolin prevented the morphological change and downregulation of E-cadherin of A549 cells induced by TGF-β1. In addition, the activation of PI3K-AKT-IκBa-NF-κB-snail pathway which leading to the decline of E-cadherin induced by TGF-β1 also attenuated under the pretreatment of luteolin. We provide the mechanisms about how luteolin attenuated the Epithelial-mesenchymal transition of A549 lung cancer cells induced by TGF-β1. This finding will strengthen the anti-cancer effects of flavonoid compounds via the regulation of migration/invasion and EMT ability of various cancer cells.
    Life sciences 10/2013; 109(2). DOI:10.1016/j.lfs.2013.10.004 · 2.30 Impact Factor
  • Source
    • "As a naturales nutrient, luteolin has beneficial effects on human body. Also, previous studies have shown luteolin exhibits as an anti-tumor agent (Byun et al., 2010), an anti-angiogenesis agent (Bagli et al., 2004), and an antimetastatic agent (Zhou et al., 2009). Luteolin affects multiple targets in cells, leading to different functions in biological processes, reports have proved that luteolin targets IGF-1R (Fang et al., 2007), TPL2 kinase (Kim et al., 2011), GSK-3b kinase (Johnson et al., 2011). "
    [Show abstract] [Hide abstract]
    ABSTRACT: In human, Aurora B is a chromosomal passenger protein that induces phosphorylation of histone and involves in spindle checkpoint and cytokinesis. Aberrant expression of Aurora B has been shown to correlate with genetic instability and carcinogenesis. In the past, Aurora B has been validated as a drug target by several studies. Here we report that the dietary flavonoid luteolin could inhibit recombinant Aurora B in radiometric activity assay (IC(50)=0.357 μM) and bind to Aurora B with a high affinity (K(D)=5.85 μM) measured by Biacore 3000. Dose-dependent down-regulation of phosphorylation on Ser10 of histone H3 was also observed in cancer cell lines after 24-h treatment, indicating that endogenous Aurora B activity was inhibited by luteolin. Furthermore, we evaluated the effects of luteolin on the survival of a panel of 23 cell lines, and found that luteolin blocked growth of HeLa cells and SW620 cells in an 8-day cell proliferation assay as well as in colony formation assay. Thus, we identified Aurora B as a novel direct target of luteolin, and our results demonstrated that targeting Aurora B by natural products may be a feasible strategy to develop low toxic anticancer agents.
    European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 03/2012; 46(5):388-96. DOI:10.1016/j.ejps.2012.03.002 · 3.01 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The main scope of this paper is to investigate the research of fuzzy PID control by utilizing the SQP (sequential quadratic programming) algorithm which is one of the constrained optimization algorithms. This paper presents a novel method to design the fuzzy PID tuners which combine the PID control and fuzzy control in order to improve the system performance for complex systems in which the normal PID controller is not suitable in such a case. The optimization algorithm is utilized to develop an optimization scheme in order to search the optimal fuzzy tuner design parameters, including the position and the shape of membership functions and the scaling factors based on the cost function. By using optimization algorithms, the fuzzy PID tuner design problem is transferred to the parameter optimal problem and the fuzzy controller design parameters are optimized such that the minimum cost function can be achieved based on the given performance index. The proposed method is applied to several numerical experiments and the results are presented to demonstrate its efficiency and performance.
    Intelligent Control and Automation, 2004. WCICA 2004. Fifth World Congress on; 07/2004
Show more