title: Mushroom Ganoderma lucidum prevents colitis-associated carcinogenesis in mice.
abstract: BACKGROUND
  Epidemiological studies suggest that mushroom intake is inversely correlated with gastric, gastrointestinal and breast cancers. We have recently demonstrated anticancer and anti-inflammatory activity of triterpene extract isolated from mushroom Ganoderma lucidum (GLT). The aim of the present study was to evaluate whether GLT prevents colitis-associated carcinogenesis in mice.
  
  
  RESULTS
  Colon carcinogenesis was induced by the food-borne carcinogen (2-Amino-1-methyl-6-phenylimidazol[4,5-b]pyridine [PhIP]) and inflammation (dextran sodium sulfate [DSS]) in mice. Mice were treated with 0, 100, 300 and 500 mg GLT/kg of body weight 3 times per week for 4 months. Cell proliferation, expression of cyclin D1 and COX-2 and macrophage infiltration was assessed by immunohistochemistry. The effect of GLT on XRE/AhR, PXR and rPXR was evaluated by the reporter gene assays. Expression of metabolizing enzymes CYP1A2, CYP3A1 and CYP3A4 in colon tissue was determined by immunohistochemistry. GLT treatment significantly suppressed focal hyperplasia, aberrant crypt foci (ACF) formation and tumor formation in mice exposed to PhIP/DSS. The anti-proliferative effects of GLT were further confirmed by the decreased staining with Ki-67 in colon tissues. PhIP/DSS-induced colon inflammation was demonstrated by the significant shortening of the large intestine and macrophage infiltrations, whereas GLT treatment prevented the shortening of colon lengths, and reduced infiltration of macrophages in colon tissue. GLT treatment also significantly down-regulated PhIP/DSS-dependent expression of cyclin D1, COX-2, CYP1A2 and CYP3A4 in colon tissue.
  
  
  CONCLUSIONS
  Our data suggest that GLT could be considered as an alternative dietary approach for the prevention of colitis-associated cancer.
authors.affiliation: Cancer Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, Indiana, United States of America. dsliva@iuhealth.org
authors.forename: Daniel
authors.initials: D
authors.lastname: Sliva
authors.forename: Jagadish
authors.initials: J
authors.lastname: Loganathan
authors.forename: Jiahua
authors.initials: J
authors.lastname: Jiang
authors.forename: Andrej
authors.initials: A
authors.lastname: Jedinak
authors.forename: John G
authors.initials: JG
authors.lastname: Lamb
authors.forename: Colin
authors.initials: C
authors.lastname: Terry
authors.forename: Lee Ann
authors.initials: LA
authors.lastname: Baldridge
authors.forename: Jiri
authors.initials: J
authors.lastname: Adamec
authors.forename: George E
authors.initials: GE
authors.lastname: Sandusky
authors.forename: Shailesh
authors.initials: S
authors.lastname: Dudhgaonkar
mesh_terms: D000631:Aminopyridines / Q000633:toxicity; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D003092:Colitis / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000178:diet therapy / Q000378:metabolism; D016264:Dextran Sulfate / Q000633:toxicity; D005770:Gastrointestinal Neoplasms / Q000150:complications / Q000178:diet therapy; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D006965:Hyperplasia / Q000139:chemically induced / Q000178:diet therapy / Q000378:metabolism; D007093:Imidazoles / Q000633:toxicity; D007249:Inflammation / Q000139:chemically induced / Q000178:diet therapy; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000178:diet therapy / Q000378:metabolism; D010936:Plant Extracts / Q000008:administration & dosage* / Q000737:chemistry; D020940:Reishi / Q000737:chemistry
chemical_list: C522525:2-amino-1-methyl-6-phenyl-1H-imidazo(4,5-b)pyridine; D000631:Aminopyridines; D000893:Anti-Inflammatory Agents; D002273:Carcinogens; D007093:Imidazoles; D010936:Plant Extracts; D016264:Dextran Sulfate