lucidenic-acid-n and Liver-Neoplasms

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-kappaB) 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-kappaB, 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-kappaB DNA-binding activities, leading to downregulation of MMP-9 expression.

Topics: Carcinoma, Hepatocellular; Cell Line, Tumor; Humans; Liver Neoplasms; MAP Kinase Signaling System; Neoplasm Invasiveness; NF-kappa B; Signal Transduction; Tetradecanoylphorbol Acetate; Transcription Factor AP-1; Triterpenes

Ganoderma lucidum is a well-known mushroom with various pharmacological effects that has been used for health and longevity purposes. The objective of this study was to investigate the anti-invasive effect of lucidenic acids isolated from a new G. lucidum strain (YK-02) against human hepatoma carcinoma (HepG(2)) cells. Triterpenoid components in the ethanol extract of G. lucidum (YK-02) were separated by means of a semi-preparative RP HPLC. Four major peaks were separated and crystallized from triterpenoids fraction, and were identified as lucidenic acids A, B, C, and N according to their spectroscopic values of (1)H NMR and MS. Treatment of the lucidenic acids (50 microM) in the presence of 200 nM phorbol 12-myristate 13-acetate (PMA) after 24 h of incubation all resulted in significant inhibitory effects on PMA-induced MMP-9 activity and invasion of HepG(2 )cells. The results indicate that the lucidenic acids isolated from G. lucidum (YK-02) are anti-invasive bioactive components on hepatoma cells.

Topics: Carcinoma, Hepatocellular; Cell Line, Tumor; Cholic Acids; Chromatography, High Pressure Liquid; Ganoderma; Humans; Liver Neoplasms; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Neoplasm Invasiveness; Terpenes; Tetradecanoylphorbol Acetate; Triterpenes