Ganoderic acid T inhibits tumor invasion in vitro and in vivo through inhibition of MMP expression.
Journal Title: Pharmacological Reports - Year 2010, Vol 62, Issue 1
Abstract
The traditional Chinese medicinal mushroom, Ganoderma lucidum, has been used in Asia for several thousand years for the prevention and treatment of a variety of diseases, including cancer. In previous work, we purified ganoderic acid T (GA-T) from G. lucidum [28]. In the present study, we investigate the functions of GA-T in terms of its effects on invasion in vitro and metastasis in vivo. A trypan blue dye exclusion assay indicates that GA-T inhibits proliferation of HCT-116 cells, a human colon carcinoma cell line. Cell aggregation and adhesion assays show that GA-T promotes homotypic aggregation and simultaneously inhibits the adhesion of HCT-116 cells to the extracellular matrix (ECM) in a dose-dependent manner.Wound healing assays indicate that GA-T also inhibits the migration of HCT-116 cells in a dose-dependent manner, and it suppresses the migration of 95-D cells, a highly metastatic human lung tumor cell line, in a dose- and time-dependent manner. In addition, GA-T inhibits the nuclear translocation of nuclear factor-kappaB (NF-kappaB) and the degradation of inhibitor of kappaB-alpha (IkappaBalpha), which leads to down-regulated expression of matrix metalloproteinase-9 (MMP-9), inducible nitric oxide synthase (iNOS), and urokinase-type plasminogen activator (uPA). Animal and Lewis Lung Carcinoma (LLC) model experiments demonstrate that GA-T suppresses tumor growth and LLC metastasis and down-regulates MMP-2 and MMP-9 mRNA expression in vivo. Taken together, these results demonstrate that GA-T effectively inhibits cancer cell invasion in vitro and metastasis in vivo, and thus it may act as a potential drug for treating cancer.
Authors and Affiliations
Nian-Hong Chen, Jian-Wen Liu, Jian-Jiang Zhong
Keywords
Related Articles
- EP ID EP144730
- DOI -
- Views 95
- Downloads 0
LC/MS/MS evaluation of cocaine and its metabolites in different brain areas, peripheral organs and plasma in cocaine self-administering rats.
We employed a cocaine intravenous self-administration model based on positive reinforcement of animals' instrumental reactions (i.e., lever pressing) rewarded by a dose of the drug. We also carried out simultaneous chara...
Pharmacokinetics of sunitinib in combination with fluoroquinolones in rabbit model.
Background: Fluoroquinolones are widely prescribed antibiotics. Ciprofloxacin is a well-known inhibitor of cytochrome P450 CYP3A4 and causes numerous drug interactions that are not found for levofloxacin and moxifloxacin...
Are the endothelial mechanisms of ACE-ls already established?
The endothelial mechanism of ACE-Is action is multifaceted. On the one hand, by inhibiting ACE, ACE-Is diminish Ang II synthesis, one of the best known active peptides. On the other hand, they modify synthesis and releas...
Type 2 diabetes mellitus: from genes to disease.
The development of type 2 diabetes (T2DM) is determined by two factors: genetics and environment. The genetic background of T2DM is undoubtedly heterogeneous. Most patients with T2DM exhibit two different defects: the im...
Influence of 825 C>T polymorphism of G protein β3 subunit gene (GNB3) on hemodynamic response during dobutamine stress echocardiography.
There is a wide interpersonal difference to dobutamine response during dobutamine stress echocardiography (DSE). The aim of this study was to determine an association between GNB3 825C>T gene polymorphism, encoding the β...