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.

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    • "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). "
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    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
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    • "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). "
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