4-Shogaol, an Active Constituent of Dietary Ginger, Inhibits Metastasis of MDA-MB-231 Human Breast Adenocarcinoma Cells by Decreasing the Repression of NF-魏B/Snail on RKIP

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• 作者：Ya-Ling Hsu ; Chung-Yi Chen ; In-Pin Lin ; Eing-Mei Tsai ; Po-Lin Kuo ; Ming-Feng Hou
• 刊名：Journal of Agricultural and Food Chemistry
• 出版年：2012
• 出版时间：January 25, 2012
• 年：2012
• 卷：60
• 期：3
• 页码：852-861
• 全文大小：619K
• 年卷期：v.60,no.3(January 25, 2012)
• ISSN：1520-5118

文摘

4-Shogaol is one of the phytoconstituents isolated from dried red ginger, which is commercially available to consumers. Some active constituents from ginger have been found to have anti-inflammatory and antioxidant effects, but studies on 4-shogaol have been relatively rare. This is the first report describing the antimetastasis activities of 4-shogaol and the possible mechanisms. This study determined that 4-shogaol inhibits the migration and invasion of MDA-MB-231 and causes mesenchymal鈥揺pithelial transition (MET). In addition, 4-shogaol suppresses the activation of NF-魏B and cell migration and invasion induced by TNF-伪. Furthermore, 4-shogaol has been shown to inhibit the phosphorylation of I魏B and the translocation of NF-魏B/Snail in MDA-MB-231. This study shows that RKIP, an inhibitory molecule of IKK, is up-regulated after 4-shogaol treatment and prolongs the inhibitory effects of 4-shogaol. Inhibition of RKIP by shRNA transfection significantly decreases the inhibitory effect of 4-shogaol on the NF-魏B/Snail pathway, together with cell migration and invasion, whereas overexpression of Snail suppresses 4-shogaol-mediated metastasis inhibition and E-cadherin upregulation. Finally, the animal model revealed that 4-shogaol effectively inhibits metastasis of MDA-MB-231 in mice. This study demonstrates that 4-shogaol may be a novel anticancer agent for the the treatment of metastasis in breast cancer.

Keywords:

4-shogaol; red ginger; metastasis; breast cancer