Iris Lavi1, Lili Nimri, Dana Levinson, Irena Peri, Yitzhak Hadar, Betty Schwartz. 1. 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.
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.
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, humancolorectal 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: Matthew Rutter; Brian Saunders; Kay Wilkinson; Steve Rumbles; Gillian Schofield; Michael Kamm; Christopher Williams; Ashley Price; Ian Talbot; Alastair Forbes Journal: Gastroenterology Date: 2004-02 Impact factor: 22.682