Inhibitory effects of ganoderma lucidum on tumorigenesis and metastasis of human hepatoma cells in cells and animal models.

Abstract

Metastasis is considered to be the major cause of death in patients with cancers, and hepatocellular carcinoma (HCC) is a highly metastatic cancer. Ganoderma lucidum , a well-known mushroom with various biological effects, is a functional food known to contain lucidenic acid. The objectives of this study were to investigate the anti-invasion effect of a lucidenic acid-rich G. lucidum extract (GLE) on human hepatoma HepG2 cells as well as the antiproliferative and antimetastatic effects of GLE in human hepatoma cells implanted into ICR-nu/nu mice. Phorbol-12-myristate-13-acetate (PMA)-induced invasion and matrix metalloproteinase (MMP)-9 expression levels of HepG2 cells were reduced by GLE treatment in a dose-dependent manner. The inhibitory effects of GLE on MMP-9 expression proceeded by inhibiting the phosphorylation of extracellular signal-regulated kinase (ERK1/2) and protein kinase B in the cytosol as well as reducing activator protein-1 and nuclear factor-kappa B levels in the nucleus of HepG2 cells. In a human tumor xenograft model, a dose-response inhibition was observed in the average size, volume, and weight of tumors upon oral administration of GLE. The number of metastatic tumor-bearing mice, the number of affected organs, and the number of tumor foci as well as the MMP-2 and -9 activities in serum of mice were also significantly suppressed by oral administration of GLE. These results suggest that the lucidenic acid-rich GLE could serve as a chemopreventive agent for the tumorigenesis and metastasis of highly invasive hepatoma cells.

• Authors: Chia-Jui Weng, Chi-Fai Chau, Gow-Chin Yen, Jiunn-Wang Liao, Deng-Hai Chen, Kuang-Dee Chen
• Journal: Journal of agricultural and food chemistry (J Agric Food Chem) Vol. 57 Issue 11 Pg. 5049-57 (Jun 10 2009) ISSN: 1520-5118 [Electronic] United States
• PMID: 19422227 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Plant Extracts

Topics

• Animals
• Antineoplastic Agents (therapeutic use)
• Carcinoma, Hepatocellular (drug therapy, pathology)
• Cell Line, Tumor
• Gene Expression Regulation, Neoplastic
• Humans
• Liver Neoplasms (drug therapy, pathology)
• Mice
• Mice, Nude
• Neoplasm Invasiveness (prevention & control)
• Neoplasm Metastasis (prevention & control)
• Plant Extracts (therapeutic use)
• Reishi (chemistry)