Advertisement

Journal of Gastroenterology

, Volume 47, Issue 5, pp 504–518 | Cite as

Glucans from the edible mushroom Pleurotus pulmonarius inhibit colitis-associated colon carcinogenesis in mice

  • Iris Lavi
  • Lili Nimri
  • Dana Levinson
  • Irena Peri
  • Yitzhak Hadar
  • Betty Schwartz
Original Article—Alimentary Tract

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.

Keywords

Apoptosis Colon Carcinogenesis Glucans Pleurotus pulmonarius 

Abbreviations

FBE

Fruiting body extract

ME

Mycelia extract

PCNA

Proliferating cell nuclear antigen

ACF

Aberrant crypt foci

Notes

Acknowledgments

This research was partially supported by a Grant from Yissum Research Development Company of the Hebrew University of Jerusalem.

Conflict of interest

The authors declare no conflicts of interest.

References

  1. 1.
    Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.PubMedCrossRefGoogle Scholar
  2. 2.
    Gunter MJ, Stolzenberg-Solomon R, Cross AJ, Leitzmann MF, Weinstein S, Wood RJ, Virtamo J, Taylor PR, Albanes D, Sinha R. A prospective study of serum C-reactive protein and colorectal cancer risk in men. Cancer Res. 2006;66:2483–7.PubMedCrossRefGoogle Scholar
  3. 3.
    Eaden JA, Abrams KR, Mayberry JF. The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut. 2001;48:526–35.PubMedCrossRefGoogle Scholar
  4. 4.
    Rutter M, Saunders B, Wilkinson K, Rumbles S, Schofield G, Kamm M, Williams C, Price A, Talbot I, Forbes A. Severity of inflammation is a risk factor for colorectal neoplasia in ulcerative colitis. Gastroenterology. 2004;126:451–9.PubMedCrossRefGoogle Scholar
  5. 5.
    Lavi I, Levinson D, Peri I, Nimri L, Hadar Y, Schwartz B. Orally administered glucans from the edible mushroom Pleurotus pulmonarius reduce acute inflammation in dextran sulfate sodium-induced experimental colitis. Br J Nutr. 2010;103:393–402.PubMedCrossRefGoogle Scholar
  6. 6.
    Borchers AT, Krishnamurthy A, Keen CL, Meyers FJ, Gershwin ME. The immunobiology of mushrooms. Exp Biol Med (Maywood). 2008;233:259–76.CrossRefGoogle Scholar
  7. 7.
    Grube BJ, Eng ET, Kao YC, Kwon A, Chen S. White button mushroom phytochemicals inhibit aromatase activity and breast cancer cell proliferation. J Nutr. 2001;131:3288–93.PubMedGoogle Scholar
  8. 8.
    Thyagarajan A, Zhu J, Sliva D. Combined effect of green tea and Ganoderma lucidum on invasive behavior of breast cancer cells. Int J Oncol. 2007;30:963–9.PubMedGoogle Scholar
  9. 9.
    Wu D, Pae M, Ren Z, Guo Z, Smith D, Meydani SN. Dietary supplementation with white button mushroom enhances natural killer cell activity in C57BL/6 mice. J Nutr. 2007;137:1472–7.PubMedGoogle Scholar
  10. 10.
    Yu CH, Kan SF, Shu CH, Lu TJ, Sun-Hwang L, Wang PS. Inhibitory mechanisms of Agaricus blazei Murill on the growth of prostate cancer in vitro and in vivo. J Nutr Biochem. 2009;20:753–64.PubMedCrossRefGoogle Scholar
  11. 11.
    Kobayashi H, Yoshida R, Kanada Y, Fukuda Y, Yagyu T, Inagaki K, Kondo T, Kurita N, Suzuki M, Kanayama N, et al. Suppressing effects of daily oral supplementation of beta-glucan extracted from Agaricus blazei Murill on spontaneous and peritoneal disseminated metastasis in mouse model. J Cancer Res Clin Oncol. 2005;131:527–38.PubMedCrossRefGoogle Scholar
  12. 12.
    Lee IS, Nishikawa A. Polyozellus multiplex, a Korean wild mushroom, as a potent chemopreventive agent against stomach cancer. Life Sci. 2003;73:3225–34.PubMedCrossRefGoogle Scholar
  13. 13.
    Green DR, Kroemer G. The pathophysiology of mitochondrial cell death. Science. 2004;305:626–9.PubMedCrossRefGoogle Scholar
  14. 14.
    Shi Y. A structural view of mitochondria-mediated apoptosis. Nat Struct Biol. 2001;8:394–401.PubMedCrossRefGoogle Scholar
  15. 15.
    Becker C, Fantini MC, Schramm C, Lehr HA, Wirtz S, Nikolaev A, Burg J, Strand S, Kiesslich R, Huber S, et al. TGF-beta suppresses tumor progression in colon cancer by inhibition of IL-6 trans-signaling. Immunity. 2004;21:491–501.PubMedCrossRefGoogle Scholar
  16. 16.
    Greten FR, Eckmann L, Greten TF, Park JM, Li ZW, Egan LJ, Kagnoff MF, Karin M. IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell. 2004;118:285–96.PubMedCrossRefGoogle Scholar
  17. 17.
    Tanaka T, de Azevedo MB, Duran N, Alderete JB, Epifano F, Genovese S, Tanaka M, Curini M. Colorectal cancer chemoprevention by 2 beta-cyclodextrin inclusion compounds of auraptene and 4′-geranyloxyferulic acid. Int J Cancer. 2010;126:830–40.PubMedCrossRefGoogle Scholar
  18. 18.
    Kerem Z, Hadar Y. Effect of manganese on preferential degradation of lignin by Pleurotus ostreatus during solid-state fermentation. Appl Environ Microbiol. 1995;61:3057–62.PubMedGoogle Scholar
  19. 19.
    Lavi I, Levinson D, Peri I, Tekoah Y, Hadar Y, Schwartz B. Chemical characterization, antiproliferative and antiadhesive properties of polysaccharides extracted from Pleurotus pulmonarius mycelium and fruiting bodies. Appl Microbiol Biotechnol. 2010;85(6):1977–90.PubMedCrossRefGoogle Scholar
  20. 20.
    Loher F, Bauer C, Landauer N, Schmall K, Siegmund B, Lehr HA, Dauer M, Schoenharting M, Endres S, Eigler A. The interleukin-1 beta-converting enzyme inhibitor pralnacasan reduces dextran sulfate sodium-induced murine colitis and T helper 1 T-cell activation. J Pharmacol Exp Ther. 2004;308:583–90.PubMedCrossRefGoogle Scholar
  21. 21.
    Schwartz B, Birk Y, Raz A, Madar Z. Nutritional-pharmacological combinations—a novel approach to reducing colon cancer incidence. Eur J Nutr. 2004;43:221–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Cooper HS, Murthy SN, Shah RS, Sedergran DJ. Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest. 1993;69:238–49.PubMedGoogle Scholar
  23. 23.
    Kim JK, Oh SM, Kwon HS, Oh YS, Lim SS, Shin HK. Anti-inflammatory effect of roasted licorice extracts on lipopolysaccharide-induced inflammatory responses in murine macrophages. Biochem Biophys Res Commun. 2006;345:1215–23.PubMedCrossRefGoogle Scholar
  24. 24.
    Riddell RH, Goldman H, Ransohoff DF, Appelman HD, Fenoglio CM, Haggitt RC, Ahren C, Correa P, Hamilton SR, Morson BC, et al. Dysplasia in inflammatory bowel disease: standardized classification with provisional clinical applications. Hum Pathol. 1983;14:931–68.PubMedCrossRefGoogle Scholar
  25. 25.
    Kodama N, Murata Y, Nanba H. Administration of a polysaccharide from Grifola frondosa stimulates immune function of normal mice. J Med Food. 2004;7:141–5.PubMedCrossRefGoogle Scholar
  26. 26.
    Yan B, Wang H, Rabbani ZN, Zhao Y, Li W, Yuan Y, Li F, Dewhirst MW, Li CY. Tumor necrosis factor-alpha is a potent endogenous mutagen that promotes cellular transformation. Cancer Res. 2006;66:11565–70.PubMedCrossRefGoogle Scholar
  27. 27.
    Kim YJ, Hong KS, Chung JW, Kim JH, Hahm KB. Prevention of colitis-associated carcinogenesis with infliximab. Cancer Prev Res (Phila). 2010;3:1314–33.CrossRefGoogle Scholar
  28. 28.
    Cohen SM, Ellwein LB. Cell proliferation in carcinogenesis. Science. 1990;249:1007–11.PubMedCrossRefGoogle Scholar
  29. 29.
    Kellett M, Potten CS, Rew DA. A comparison of in vivo cell proliferation measurements in the intestine of mouse and man. Epithelial Cell Biol. 1992;1:147–55.PubMedGoogle Scholar
  30. 30.
    McGarrity TJ, Peiffer LP, Colony PC. Cellular proliferation in proximal and distal rat colon during 1, 2-dimethylhydrazine-induced carcinogenesis. Gastroenterology. 1988;95:343–8.PubMedGoogle Scholar
  31. 31.
    Barnes CJ, Cameron IL, Hardman WE, Lee M. Non-steroidol anti-inflammatory drug effect on crypt cell proliferation and apoptosis during initiation of rat colon carcinogenesis. Br J Cancer. 1998;77:573–80.PubMedCrossRefGoogle Scholar
  32. 32.
    Essers J, Theil AF, Baldeyron C, van Cappellen WA, Houtsmuller AB, Kanaar R, Vermeulen W. Nuclear dynamics of PCNA in DNA replication and repair. Mol Cell Biol. 2005;25:9350–9.PubMedCrossRefGoogle Scholar
  33. 33.
    Fesik SW. Promoting apoptosis as a strategy for cancer drug discovery. Nat Rev Cancer. 2005;5:876–85.PubMedCrossRefGoogle Scholar
  34. 34.
    Fullerton SA, Samadi AA, Tortorelis DG, Choudhury MS, Mallouh C, Tazaki H, Konno S. Induction of apoptosis in human prostatic cancer cells with beta-glucan (Maitake mushroom polysaccharide). Mol Urol. 2000;4:7–13.PubMedGoogle Scholar
  35. 35.
    Hu H, Zhang Z, Lei Z, Yang Y, Sugiura N. Comparative study of antioxidant activity and antiproliferative effect of hot water and ethanol extracts from the mushroom Inonotus obliquus. J Biosci Bioeng. 2009;107:42–8.PubMedCrossRefGoogle Scholar
  36. 36.
    Zhang M, Chiu LC, Cheung PC, Ooi VE. Growth-inhibitory effects of a beta-glucan from the mycelium of Poria cocos on human breast carcinoma MCF-7 cells: cell-cycle arrest and apoptosis induction. Oncol Rep. 2006;15:637–43.PubMedGoogle Scholar
  37. 37.
    Joo YE, Karrasch T, Muhlbauer M, Allard B, Narula A, Herfarth HH, Jobin C. Tomato lycopene extract prevents lipopolysaccharide-induced NF-kappaB signaling but worsens dextran sulfate sodium-induced colitis in NF-kappaBEGFP mice. PLoS One. 2009;4:e4562.PubMedCrossRefGoogle Scholar
  38. 38.
    Paul G, Bataille F, Obermeier F, Bock J, Klebl F, Strauch U, Lochbaum D, Rummele P, Farkas S, Scholmerich J, et al. Analysis of intestinal haem-oxygenase-1 (HO-1) in clinical and experimental colitis. Clin Exp Immunol. 2005;140:547–55.PubMedCrossRefGoogle Scholar
  39. 39.
    Hengartner MO. The biochemistry of apoptosis. Nature. 2000;407:770–6.PubMedCrossRefGoogle Scholar
  40. 40.
    Yang J, Liu X, Bhalla K, Kim CN, Ibrado AM, Cai J, Peng TI, Jones DP, Wang X. Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. Science. 1997;275:1129–32.PubMedCrossRefGoogle Scholar
  41. 41.
    Matsuyama S, Llopis J, Deveraux QL, Tsien RY, Reed JC. Changes in intramitochondrial and cytosolic pH: early events that modulate caspase activation during apoptosis. Nat Cell Biol. 2000;2:318–25.PubMedCrossRefGoogle Scholar
  42. 42.
    Cai J, Jones DP. Superoxide in apoptosis. Mitochondrial generation triggered by cytochrome c loss. J Biol Chem. 1998;273:11401–4.PubMedCrossRefGoogle Scholar
  43. 43.
    Green DR, Reed JC. Mitochondria and apoptosis. Science. 1998;281:1309–12.PubMedCrossRefGoogle Scholar
  44. 44.
    Luo X, Budihardjo I, Zou H, Slaughter C, Wang X. Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors. Cell. 1998;94:481–90.PubMedCrossRefGoogle Scholar
  45. 45.
    Gross A, McDonnell JM, Korsmeyer SJ. BCL-2 family members and the mitochondria in apoptosis. Genes Dev. 1999;13:1899–911.PubMedCrossRefGoogle Scholar
  46. 46.
    Wei MC, Zong WX, Cheng EH, Lindsten T, Panoutsakopoulou V, Ross AJ, Roth KA, MacGregor GR, Thompson CB, Korsmeyer SJ. Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science. 2001;292:727–30.PubMedCrossRefGoogle Scholar
  47. 47.
    Zhu T, Guo J, Collins L, Kelly J, Xiao ZJ, Kim SH, Chen CY. Phellinus linteus activates different pathways to induce apoptosis in prostate cancer cells. Br J Cancer. 2007;96:583–90.PubMedCrossRefGoogle Scholar
  48. 48.
    Zong WX, Lindsten T, Ross AJ, MacGregor GR, Thompson CB. BH3-only proteins that bind pro-survival Bcl-2 family members fail to induce apoptosis in the absence of Bax and Bak. Genes Dev. 2001;15:1481–6.PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2011

Authors and Affiliations

  • Iris Lavi
    • 1
  • Lili Nimri
    • 1
  • Dana Levinson
    • 2
  • Irena Peri
    • 1
  • Yitzhak Hadar
    • 2
  • Betty Schwartz
    • 1
  1. 1.Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and EnvironmentThe Hebrew University of JerusalemRehovotIsrael
  2. 2.Department of Plant Pathology and Microbiology, The Robert H. Smith Faculty of Agriculture, Food and EnvironmentThe Hebrew University of JerusalemRehovotIsrael

Personalised recommendations