Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/62197
標題: Lucidenic acid inhibits PMA-induced invasion of human hepatoma cells through inactivating MAPK/ERK signal transduction pathway and reducing binding activities of NF-kappa B and AP-1
作者: Weng, C.J.
顏國欽
Chau, C.F.
Hsieh, Y.S.
Yang, S.F.
Yen, G.C.
周志輝
關鍵字: hepatocellular-carcinoma cells
iv collagenase expression
ganoderma-lucidum
gene-expression
protein-kinase
matrix
metalloproteinases
hepatocarcinoma cells
c-jun
mmp-9
activation
期刊/報告no:: Carcinogenesis, Volume 29, Issue 1, Page(s) 147-156.
摘要: Ganoderma lucidum has been reported to be associated with suppressed motility, invasion and metastasis of several types of cancers, but its mechanism of action remains unclear. In our previous study, lucidenic acids A, B, C and N were isolated from a new strain of G.lucidum and all of them were found to have potential anti-invasive activity on phorbol-12-myristate-13-acetate (PMA)-induced HepG(2) cells by suppressing the matrix metalloproteinase (MMP)-9 activity. Here, the lucidenic acid B (LAB) was used to explore its mechanisms underlying MMP-9 expression of HepG(2) cells. The results showed that the LAB suppressed PMA-induced MMP-9 activity in a dose-dependent transcriptional level. The suppression of PMA-induced MMP-9 expression of HepG(2) cells by LAB was through inactivating phosphorylation of extracellular signal-regulated kinase (ERK) 1/2. The treatment of mitogen-activated protein kinase kinase (MEK) inhibitors (PD98059 and U0126) and LAB to HepG(2) cells could result in a synergistic reduction on the MMP-9 expression along with an inhibition on cell invasion. Moreover, LAB also strongly inhibited PMA-stimulated nuclear factor-kappa B (NF-kappa B) and activator protein-1 (AP-1) DNA-binding activities of HepG(2) cells in dose-dependent manners. A dose-dependent inhibition on protein levels of NF-kappa B, c-Jun and c-Fos in nuclear by LAB treatment was further observed. In conclusion, we demonstrated that the anti-invasive effects of the LAB on the PMA-induced HepG(2) cells might be through inhibiting the phosphorylation of ERK1/2 and reducing AP-1 and NF-kappa B DNA-binding activities, leading to downregulation of MMP-9 expression.
URI: http://hdl.handle.net/11455/62197
ISSN: 0143-3334
文章連結: http://dx.doi.org/10.1093/carcin/bgm261
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