Anti-invasion effects of 6-shogaol and 6-gingerol, two active components in ginger, on human hepatocarcinoma cells.
METHODS
Hepatocellular carcinoma is the most common type of liver cancer and is highly metastatic. Metastasis is considered to be the major cause of death in cancer patients. Ginger is a natural dietary rhizome with anti-oxidative, anti-inflammatory, and anti-carcinogenic activities. The aims of this study were to evaluate the anti-invasion activity of 6-shogaol and 6-gingerol, two compounds found in ginger, on hepatoma cells.


RESULTS
The migratory and invasive abilities of phorbol 12-myristate 13-acetate (PMA)-treated HepG2 and PMA-untreated Hep3B cells were both reduced in a dose-dependent manner by treatment with 6-shogaol and 6-gingerol. Upon incubation of PMA-treated HepG2 cells and PMA-untreated Hep3B cells with 6-shogaol and 6-gingerol, matrix metalloproteinase (MMP)-9 activity decreased, whereas the expression of tissue inhibitor metalloproteinase protein (TIMP)-1 increased in both cell types. Additionally, urokinase-type plasminogen activator activity was dose-dependently decreased in Hep3B cells after incubation with 6-shogaol for 24 h. Analysis with semi-quantitative reverse transcription-PCR showed that the regulation of MMP-9 by 6-shogaol and 6-gingerol and the regulation of TIMP-1 by 6-shogaol in Hep3B cells may on the transcriptional level.


CONCLUSIONS
These results suggest that 6-shogaol and 6-gingerol might both exert anti-invasive activity against hepatoma cells through regulation of MMP-9 and TIMP-1 and that 6-shogaol could further regulate urokinase-type plasminogen activity.
Department of Food Science and Biotechnology, National Chung Hsing University, Taichung, Taiwan.
Chia-Jui
CJ
Weng
Cheng-Feng
CF
Wu
Hsiao-Wen
HW
Huang
Chi-Tang
CT
Ho
Gow-Chin
GC
Yen
D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D002396:Catechols / Q000494:pharmacology*; D005233:Fatty Alcohols / Q000494:pharmacology*; D020939:Zingiber officinale / Q000737:chemistry; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D015398:Signal Transduction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
D002396:Catechols; D005233:Fatty Alcohols; D019715:Tissue Inhibitor of Metalloproteinase-1; C040115:shogaol; C007845:gingerol; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9