Journal
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
Volume 60, Issue 3, Pages 852-861Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jf2052515
Keywords
4-shogaol; red ginger; metastasis; breast cancer
Funding
- National Science Concil of Taiwan [NSC 99-2628-B-037-006-MY3]
- Excellence for Cancer Research Center
- Department of Health, Executive Yuan, Taipei, Taiwan [DOH101-TD-C-111-002]
- Kaohsiung Medical University Hospital [KMUH99-9I04]
- Kaohsiung Medical University Foundation [KMUER008]
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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 inesenchyrnal-epithelial transition (MET). In addition, 4-shogaol suppresses the activation of NF-kappa B and cell migration and invasion induced by TNF-alpha. Furthermore, 4-shogaol has been shown to inhibit the phosphorylation of IKB and the translocation of NF-kappa B/Suail in MDA-MB-231. This study shows that RKIP, an inhibitory molecule of IKK, is up-regulated after 4-shogaol trealment and prolongs the inhibitory effects of 4-shogaol. Inhibition of RKIP by shRNA transfection significantly decreases the inhibitory effect of 4-shogaol on the NE-KB/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-shegaol 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.
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