期刊
MOLECULAR NUTRITION & FOOD RESEARCH
卷 56, 期 8, 页码 1304-1314出版社
WILEY
DOI: 10.1002/mnfr.201200173
关键词
Angiogenesis; 6-Gingerol; Invasion; Matrix metalloproteinase; 6-Shogaol
资金
- National Science Council, Taiwan, R.O.C. [NSC99-2628-B005-002-MY3]
- Ministry of Education, Taiwan, R.O.C.
Scope We previously demonstrated that 6-shogaol and 6-gingerol, two active compounds in ginger (Zingiber officinale), possess antiinvasive activity against highly metastatic hepatoma cells. The aims of this study were to evaluate the inhibitory effect and molecular mechanism underlying the transcription and translation of matrix metalloproteinases (MMPs) and urokinase-type plasminogen activator (uPA) in Hep3B cells as well as the antiangiogenic activity of 6-gingerol and 6-shogaol. Methods and results By gelatin zymography and luciferase reporter gene assays, we found that 6-gingerol and 6-shogaol regulate MMP-2/-9 transcription. Moreover, 6-gingerol directly decreased expression of uPA, but the 6-shogaol-mediated decrease in uPA was accompanied by up-regulation of plasminogen activator inhibitor (PAI)-1. 6-Gingerol and 6-shogaol concentrations of >= 10 mu M and >= 2.5 mu M, respectively, significantly inhibited the phosphorylation of mitogen-activated protein kinase (MAPK) and PI3K/Akt signaling, the activation of NF-kappa B, and the translocation of NF-kappa B and STAT3. Incubation of 6-gingerol or 6-shogaol with human umbilical vein endothelial cells or rat aortas significantly attenuated tube formation. Conclusion 6-Shogaol and 6-gingerol effectively inhibit invasion and metastasis of hepatocellular carcinoma through diverse molecular mechanisms, including inhibition of the MAPK and PI3k/Akt pathways and NF-kappa B and STAT3 activities to suppress expression of MMP-2/-9 and uPA and block angiogenesis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据