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篇名/題名: | Lucidenic acid inhibits PMA-induced invasion of human hepatoma cells through inactivating MAPK/ERK signal transduction pathway and reducing binding activities of NF-kappaB and AP-1 |
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 HepG2 cells by suppressing the matrix metalloproteinase (MMP)-9 activity. Here, the lucidenic acid B was used to explore its mechanisms underlying MMP-9 expression of HepG2 cells. The results showed that the lucidenic acid B suppressed PMA-induced MMP-9 activity in a dose-dependent transcriptional level. The suppression of PMA-induced MMP-9 expression of HepG2 cells by lucidenic acid B was through inactivating phosphorylation of ERK1/2. The treatment of MEK inhibitors (PD98059 and U0126) and lucidenic acid B to HepG2 cells could result in a synergistic reduction on the MMP-9 expression along with an inhibition on cell invasion. Moreover, lucidenic acid B also strongly inhibited PMA-stimulated nuclear factor-kappa B (NF-B) and activator protein-1 (AP-1) DNA binding activities of HepG2 cells in dose-dependent manners. A dose-dependent inhibition on protein levels of NF-B, c-Jun and c-Fos in nuclear by lucidenic acid B treatment was further observed. In conclusion, we demonstrated that the anti-invasive effects of the lucidenic acid B on the PMA-induced HepG2 cells might be through inhibiting the phosphorylation of ERK1/2 and reducing AP-1 and NF-B DNA binding activities, leading to down-regulation of MMP-9 expression. |
類型: | 期刊論文 |
西元出版年: | 2008 |
著作語言: | zh-TW |
作者: | Weng,Chia Jui、Chau,Chi Fai、Hsieh, Yih Shou、Yang,Shun Fa、Yen,Gow Chin
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學校系所: | 生活服務產業系 |
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