Skip to main content
SpringerLink
Log in

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

  • Original Article—Alimentary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

An Erratum to this article was published on 07 September 2012

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Abbreviations

FBE:

Fruiting body extract

ME:

Mycelia extract

PCNA:

Proliferating cell nuclear antigen

ACF:

Aberrant crypt foci

References

  1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  3. Eaden JA, Abrams KR, Mayberry JF. The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut. 2001;48:526–35.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  6. Borchers AT, Krishnamurthy A, Keen CL, Meyers FJ, Gershwin ME. The immunobiology of mushrooms. Exp Biol Med (Maywood). 2008;233:259–76.

    Article  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  13. Green DR, Kroemer G. The pathophysiology of mitochondrial cell death. Science. 2004;305:626–9.

    Article  PubMed  CAS  Google Scholar 

  14. Shi Y. A structural view of mitochondria-mediated apoptosis. Nat Struct Biol. 2001;8:394–401.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  22. Cooper HS, Murthy SN, Shah RS, Sedergran DJ. Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest. 1993;69:238–49.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  28. Cohen SM, Ellwein LB. Cell proliferation in carcinogenesis. Science. 1990;249:1007–11.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  33. Fesik SW. Promoting apoptosis as a strategy for cancer drug discovery. Nat Rev Cancer. 2005;5:876–85.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  39. Hengartner MO. The biochemistry of apoptosis. Nature. 2000;407:770–6.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  42. Cai J, Jones DP. Superoxide in apoptosis. Mitochondrial generation triggered by cytochrome c loss. J Biol Chem. 1998;273:11401–4.

    Article  PubMed  CAS  Google Scholar 

  43. Green DR, Reed JC. Mitochondria and apoptosis. Science. 1998;281:1309–12.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  45. Gross A, McDonnell JM, Korsmeyer SJ. BCL-2 family members and the mitochondria in apoptosis. Genes Dev. 1999;13:1899–911.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

  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

    Iris Lavi, Lili Nimri, Irena Peri & Betty Schwartz

  2. Department of Plant Pathology and Microbiology, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel

    Dana Levinson & Yitzhak Hadar

Authors
  1. Iris Lavi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lili Nimri
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dana Levinson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Irena Peri
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yitzhak Hadar
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Betty Schwartz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Betty Schwartz.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lavi, I., Nimri, L., Levinson, D. et al. Glucans from the edible mushroom Pleurotus pulmonarius inhibit colitis-associated colon carcinogenesis in mice. J Gastroenterol 47, 504–518 (2012). https://doi.org/10.1007/s00535-011-0514-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00535-011-0514-7

Keywords

Search

Navigation