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

Ginger is an herb. The rhizome (underground stem) is used as a spice and also as a medicine. It can be used fresh, dried and powdered, or as a juice or oil. Ginger is commonly used to treat various types of "stomach problems," including motion sickness, morning sickness, colic, upset stomach, gas, diarrhea, nausea and vomiting after surgery, as well as loss of appetite. Other uses include treating upper respiratory tract infections, cough, and bronchitis.

Hsu YL, Chen CY, Lin IP, Tsai EM, Kuo PL, Hou MF. 4-Shogaol, an active constituent of dietary ginger, inhibits metastasis of MDA-MB-231 human breast adenocarcinoma cells by decreasing the repression of NF-?B/Snail on RKIP. 1. J Agric Food Chem. 2012 Jan 25;60(3):852-61. Epub 2012 Jan 13.

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-epithelial transition (MET). In addition, 4-shogaol suppresses the activation of NF-?B and cell migration and invasion induced by TNF-?. Furthermore, 4-shogaol has been shown to inhibit the phosphorylation of I?B and the translocation of NF-?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-?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.