title: Ganoderic acid T inhibits tumor invasion in vitro and in vivo through inhibition of MMP expression.
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.affiliation: Key Laboratory of Microbial Metabolism, Ministry of Education, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dong-Chuan Road, Minhang, Shanghai 200240, China. nhchen1224@yahoo.com.cn
authors.forename: Nian-Hong
authors.initials: NH
authors.lastname: Chen
authors.forename: Jian-Wen
authors.initials: JW
authors.lastname: Liu
authors.forename: Jian-Jiang
authors.initials: JJ
authors.lastname: Zhong
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D002449:Cell Aggregation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007810:Lanosterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000517:prevention & control; D011480:Protease Inhibitors / Q000494:pharmacology*; D012334:RNA, Neoplasm / Q000096:biosynthesis; D020940:Reishi / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000903:Antibiotics, Antineoplastic; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D012334:RNA, Neoplasm; C550530:ganoderic acid T; D007810:Lanosterol; D020782:Matrix Metalloproteinases; D020780:Matrix Metalloproteinase 9