Molecular mechanism inhibiting human hepatocarcinoma cell invasion by 6-shogaol and 6-gingerol
Article first published online: 20 JUN 2012
© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 56, Issue 8, pages 1304–1314, August 2012
How to Cite
Weng, C.-J., Chou, C.-P., Ho, C.-T. and Yen, G.-C. (2012), Molecular mechanism inhibiting human hepatocarcinoma cell invasion by 6-shogaol and 6-gingerol. Mol. Nutr. Food Res., 56: 1304–1314. doi: 10.1002/mnfr.201200173
- Issue published online: 10 AUG 2012
- Article first published online: 20 JUN 2012
- Manuscript Accepted: 25 APR 2012
- Manuscript Revised: 20 APR 2012
- Manuscript Received: 28 MAR 2012
- National Science Council. Grant Number: NSC99-2628-B005-002-MY3
- Matrix metalloproteinase;
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 μM and ≥2.5 μM, respectively, significantly inhibited the phosphorylation of mitogen-activated protein kinase (MAPK) and PI3K/Akt signaling, the activation of NF-κB, and the translocation of NF-κB and STAT3. Incubation of 6-gingerol or 6-shogaol with human umbilical vein endothelial cells or rat aortas significantly attenuated tube formation.
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-κB and STAT3 activities to suppress expression of MMP-2/-9 and uPA and block angiogenesis.