title: Glucans from the edible mushroom Pleurotus pulmonarius inhibit colitis-associated colon carcinogenesis in mice.
abstract: BACKGROUND
  We have recently demonstrated that polysaccharides from fruiting body extract (FBE) or mycelia extract (ME) of the edible mushroom Pleurotus pulmonarius exert antiproliferative effects in intestinal cells and an anti-inflammatory effect in a dextran sulfate sodium (DSS) mouse model of acute colitis. The aim of this study was to assess the role of fungal FBE and ME in colon carcinogenesis.
  
  
  METHODS
  In vitro, human colorectal cancer cells were treated with FBE and ME and analyzed for inflammation response, for markers of apoptosis, and for cell-cycle progression. In vivo, FBE and ME were tested in a mouse model of colitis-associated colorectal carcinogenesis induced by cyclic treatments with DSS and azoxymethane. Treated mice were fed a daily diet containing 2 or 20 mg FBE or ME per mouse for 80 days.
  
  
  RESULTS
  In vitro, FBE and ME induced apoptosis in a dose-responsive manner and modulated the expression of Bcl-2, Bax, and cytochrome c, and blocked tumor necrosis factor (TNF)-α-induced inhibitor of nuclear factor (NF) (Iκ)-Bα degradation and NF-κB nuclear translocation. In vivo, dietary administration of FBE and ME significantly reduced the formation of aberrant crypt foci, which precedes colorectal cancer, and of microadenomas. The treatments significantly lowered the expression of proliferating cell nuclear antigen and increased the number of cells undergoing apoptosis in the colon. Additionally, FBE and ME inhibited the expression of the proinflammatory cytokine TNF-α in colonic tissue.
  
  
  CONCLUSIONS
  We conclude that P. pulmonarius FBE and ME inhibit colitis-associated colon carcinogenesis induced in mice through the modulation of cell proliferation, induction of apoptosis, and inhibition of inflammation.
authors.affiliation: Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, P.O. Box 12, 76100, Rehovot, Israel.
authors.forename: Iris
authors.initials: I
authors.lastname: Lavi
authors.forename: Lili
authors.initials: L
authors.lastname: Nimri
authors.forename: Dana
authors.initials: D
authors.lastname: Levinson
authors.forename: Irena
authors.initials: I
authors.lastname: Peri
authors.forename: Yitzhak
authors.initials: Y
authors.lastname: Hadar
authors.forename: Betty
authors.initials: B
authors.lastname: Schwartz
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003092:Colitis / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D048690:Fruiting Bodies, Fungal / Q000737:chemistry; D005936:Glucans / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D025282:Mycelium / Q000737:chemistry; D008517:Phytotherapy / Q000379:methods*; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D020076:Pleurotus / Q000737:chemistry*; D014407:Tumor Cells, Cultured
chemical_list: D005936:Glucans; D010936:Plant Extracts