Abstract

Modern medicine successfully uses multiple immunomodulators of natural origin, that can affect biological reactions and support body’s natural defense mechanisms including antitumor activities. Among them is a group of products derived from fungi, including schizophyllan, lentinan, polysaccharide Krestin (PSK), and polysaccharidepeptide (PSP). Present paper is focused on polysaccharidepeptide, which due to the negligible toxicity and numerous benefits for health, is increasingly used in China and Japan as an adjuvant in the treatment of cancer. PSP is a protein-polisaccharide complex with a molecular weight 100 kDa derived from Coriolus versicolor mushroom. The results of numerous studies and clinical trials confirm that it inhibits the growth of cancer cells in in vitro and in vivo settings as well as decreases cancer treatment-related adverse side effects such as fatigue, loss of appetite, nausea, vomiting, and pain. PSP is able to restore weakened immune response observed in patients with cancer during chemotherapy. Its anti-tumor effects seemed to be mediated through immunomodulatory regulation. PSP stimulates cells of the immune system, induces synthesis of cytokines such as interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α), eicosanoids including prostaglandin E2 (PGE2), histamine, reactive oxygen species and nitrogen mediators. There is a growing interest in understanding the mechanisms of PSP action. Because of its unique properties and safety, PSP may become a widely used therapeutic agent in the near future.

References

• 1. Brown D.C., Reetz J.: Single agent polysaccharopeptide delaysmetastases and improves survival in naturally occurring hemangiosarcoma.Evid. Based Complement. Alternat. Med., 2012; 2012: 384301
  Google Scholar
• 2. Chan S.L., Yeung J.H.: Effects of polysaccharide peptide (PSP)from Coriolus versicolor on the pharmacokinetics of cyclophosphamidein the rat and cytotoxicity in HepG2 cells. Food Chem. Toxicol.,2006; 44: 689-694
  Google Scholar
• 3. Chan S.L., Yeung J.H.: Modulation of antipyrine clearance by polysaccharidepeptide (PSP) isolated from Coriolus versicolor in therat. Food Chem. Toxicol., 2006; 44: 1607-1612
  Google Scholar
• 4. Chan S.L., Yeung J.H.: Polysaccharide peptides from COV-1 strainof Coriolus versicolor induce hyperalgesia via inflammatory mediatorrelease in the mouse. Life Sci., 2006; 78: 2463-2470
  Google Scholar
• 5. Cheng K.F., Leung P.C.: General review of polysaccharopeptides(PSP) from C. versicolor: Pharmacological and clinical studies. CancerTher., 2008; 6: 117-130
  Google Scholar
• 6. Chow L.W., Lo C.S., Loo W.T., Hu X.C., Sham J.S.: Polysaccharidepeptide mediates apoptosis by up-regulating p21 gene and down–regulating cyclin D1 gene. Am. J. Chin. Med., 2003; 31: 1-9
  Google Scholar
• 7. Chu K.K., Ho S.S., Chow A.H.: Coriolus versicolor: a medicinalmushroom with promising immunotherapeutic values. J. Clin. Pharmacol.,2002; 42: 976-984
  Google Scholar
• 8. Cui J., Chisti Y.: Polysaccharopeptides of Coriolus versicolor: physiologicalactivity, uses, and production. Biotechnol. Adv., 2003; 21:109-122
  Google Scholar
• 9. Dempsey P.W., Vaidya S.A., Cheng G.: The art of war: Innate andadaptive immune responses. Cell. Mol. Life Sci., 2003; 60: 2604-2621
  Google Scholar
• 10. Dong Y., Kwan C.Y., Chen Z.N., Yang M.M.: Antitumor effectsof a refined polysaccharide peptide fraction isolated from Coriolusversicolor: in vitro and in vivo studies. Res. Commun. Mol. Pathol.Pharmacol., 1996; 92: 140-148
  Google Scholar
• 11. Handbook of Biologically Active Peptides, red.: Kastin A.J., AcademicPress, London 2013; 180-186
  Google Scholar
• 12. Ho C.Y., Kim C.F., Leung K.N., Fung K.P., Tse T.F., Chan H., LauC.B.: Differential anti-tumor activity of Coriolus versicolor (Yunzhi)extract through p53 – and/or Bcl-2-dependent apoptotic pathwayin human breast cancer cells. Cancer Biol. Ther., 2005; 4: 638-644
  Google Scholar
• 13. Ho J.C., Konerding M.A., Gaumann A., Groth M., Liu W.K.: Fungalpolysaccharopeptide inhibits tumor angiogenesis and tumor growthin mice. Life Sci., 2004; 75: 1343-1356
  Google Scholar
• 14. Hsieh T.C., Kunicki J., Darzynkiewicz Z., Wu J.M.: Effects ofextracts of Coriolus versicolor (I’m-YunityTM) on cell-cycle progressionand expression of interleukins-1β, – 6, and – 8 in promyelocyticHL-60 leukemic cells and mitogenically stimulated andnonstimulated human lymphocytes. J. Altern. Complement. Med.,2002; 8: 591-602
  Google Scholar
• 15. Hsieh T.C., Wu J.M.: Cell growth and gene modulatory activitiesof Yunzhi (Windsor Wunxi) from mushroom Trametes versicolorin androgen-dependent and androgen-insensitive human prostatecancer cells. Int. J. Oncol., 2001; 18: 81-88
  Google Scholar
• 16. Kanazawa M., Yoshihara K., Abe H., Iwadate M., Watanabe K.,Suzuki S., Endoh Y., Takita K., Sekikawa K., Takenoshita S., Ogata T.,Ohto H.: Effects of PSK on T and dendritic cells differentiation in gastricor colorectal cancer patients. Anticancer Res., 2005; 25: 443-449
  Google Scholar
• 17. Kidd P.M.: The use of mushroom glucans and proteoglycans incancer treatment. Altern. Med. Rev., 2000; 5: 4-27
  Google Scholar
• 18. Lau C.B., Ho C.Y., Kim C.F., Leung K.N., Fung K.P., Tse T.F., ChanH.H., Chow M.S.: Cytotoxic activities of Coriolus versicolor (Yunzhi)extract on human leukemia and lymphoma cells by induction ofapoptosis. Life Sci., 2004; 75: 797-808
  Google Scholar
• 19. Lee C.L., Sit W.H., Jiang P.P., So I.W., Wan J.M.: Polysaccharopeptidemimics ciclosporin-mediated Th1/Th2 cytokine balance forsuppression of activated human T cell proliferation by MAPKp38 andSTAT5 pathways. J. Pharm. Pharmacol., 2008; 60: 1491-1499
  Google Scholar
• 20. Lee C.L., Yang X., Wan J.M.: The culture duration affects theimmunomodulatory and anticancer effect of polysaccharopeptidederived from Coriolus versicolor. Enzyme Microb. Technol., 2006;38: 14-21
  Google Scholar
• 21. Li W., Liu M., Lai S., Xu C., Lu F., Xiao X., Bao Y.: Immunomodulatoryeffects of polysaccharopeptide (PSP) in human PBMC throughregulation of TRAF6/TLR immunosignal-transduction pathways.Immunopharmacol. Immunotoxicol., 2010; 32: 576-584
  Google Scholar
• 22. Lin I.H., Hau D.M., Chang Y.H.: Restorative effect of Coriolus versicolorpolysaccharides against gamma-irradiation-induced spleeninjury in mice. Acta Pharmacol. Sinica, 1996; 17: 102-104
  Google Scholar
• 23. Liu W.K., Ng T.B., Sze S.F., Tsui K.W.: Activation of peritonealmacrophages by polysaccharopeptide from the mushroom Coriolusversicolor. Immunopharmacology, 1993; 26: 139-146
  Google Scholar
• 24. Liu W.K., Ooi V.E., Liu W.K., Chang S.T.: Immunomodulation andantitumor activity of polysaccharide-protein complex from the culturefiltrates of a local edible mushroom, Tricholoma lobayense. Gen.Pharmacol., 1996; 27: 621-624
  Google Scholar
• 25. Luk S.U., Lee T.K., Liu J., Lee D.T., Chiu Y.T., Ma S., Ng I.O., WongY.C., Chan F.L., Ling M.T.: Chemopreventive effect of PSP throughtargeting of prostate cancer stem cell-like population. PLoS One,2011; 6: e19804
  Google Scholar
• 26. Madej G.: Chemioterapia onkologiczna dorosłych i dzieci. WydawnictwoLekarskie PZWL, Warszawa 1999
  Google Scholar
• 27. Mao X.W., Archambeau J.O., Gridley D.S.: Immunotherapy withlow-dose interleukin-2 and a polysaccharopeptide derived fromCoriolus versicolor. Cancer Biother. Radiopharm., 1996; 11: 393-403
  Google Scholar
• 28. Mao X.W., Green L.M., Gridley D.S.: Evaluation of polysaccharopeptideeffects against C6 glioma in combination with radiation.Oncology, 2001; 61: 243-253
  Google Scholar
• 29. Ng T.B.: A review of research on the protein-bound polysaccharide(polysaccharopeptide, PSP) from the mushroom Coriolus versicolor(Basidiomycetes: Polyporaceae). Gen. Pharmacol., 1998; 30: 1-4
  Google Scholar
• 30. Ng T.B., Chan W.Y.: Polysaccharopeptide from the mushroomCoriolus versicolor possesses analgesic activity but does not produceadverse effects on female reproductive or embryonic developmentin mice. Gen. Pharmacol., 1997; 29: 269-273
  Google Scholar
• 31. Qian Z.M., Xu M.F., Tang P.L.: Polysaccharide peptide (PSP) restoresimmunosuppression induced by cyclophosphamide in rats.Am. J. Chin. Med., 1997; 25: 27-35
  Google Scholar
• 32. Ren L., Perera C., Hemar Y.: Antitumor activity of mushroompolysaccharides: a review. Food Funct., 2012; 3: 1118-1130
  Google Scholar
• 33. Renton K.W.: Alteration of drug biotransformation and eliminationduring infection and inflammation. Pharmacol. Ther., 2001;92: 147-163
  Google Scholar
• 34. Saluk-Juszczak J., Królewska K.: β-glucan from saccharomycescerevisiae – the natura stimulator of immune system. Kosmos,2010; 59: 151-160
  Google Scholar
• 35. Schepetkin I.A., Quinn M.T.: Botanical polysaccharides: macrophageimmunomodulation and therapeutic potential. Int. Immunopharmacol.,2006; 6: 317-333
  Google Scholar
• 36. Sekhon B.K., Sze D.M., Chan W.K., Fan K., Li G.Q., Moore D.E.,Roubin R.H.: PSP activates monocytes in resting human peripheralblood mononuclear cells: immunomodulatory implications for cancertreatment. Food Chem., 2013; 138: 2201-2209
  Google Scholar
• 37. Sze D.M., Chan G.C.: Supplements for immune enhancementin hematologic malignancies. Hematology Am. Soc. Hematol. Educ.Program, 2009; 2009: 313-319
  Google Scholar
• 38. Tavares E., Maldonado R., Ojeda M.L., Miñano F.J.: Circulating inflammatorymediators during start of fever in differential diagnosisof gram-negative and gram-positive infections in leukopenic rats.Clin. Diagn. Lab. Immunol., 2005; 12: 1085-1093
  Google Scholar
• 39. Tsang K.W., Lam C.L., Yan C., Mak J.C., Ooi G.C., Ho J.C., LamB., Man R., Sham J.S., Lam W.K.: Coriolus versicolor polysaccharidepeptide slows progression of advanced non-small cell lung cancer.Respir. Med., 2003; 97: 618-624
  Google Scholar
• 40. Tzianabos A.O.: Polysaccharide immunomodulators as therapeuticagents: structural aspects and biologic function. Clin. Microbiol.Rev., 2000; 13: 523-533
  Google Scholar
• 41. Wang H.X., Ng T.B., Liu W.K., Ooi V.E., Chang S.T.: Polysaccharide–peptide complexes from the cultured mycelia of the mushroom Coriolusversicolor and their culture medium activate mouse lymphocytesand macrophages. Int. J. Biochem. Cell Biol., 1996; 28: 601-607
  Google Scholar
• 42. Wei W.S., Tan J.Q., Guo F., Ghen H.S., Zhou Z.Y., Zhang Z.H., GuiL.: Effects of Coriolus versicolor polysaccharides on superoxide dismutaseactivities in mice. Acta Pharmacol. Sinica, 1996; 17: 174-178
  Google Scholar
• 43. Wojewoda W.: Checklist of Polish Larger Basidiomycetes. Krytycznalista wielkoowocnikowych grzybów podstawkowych Polski.W. Szafer Institute of Botany, Polish Academy of Sciences, Kraków2003
  Google Scholar
• 44. Wynn T.A., Chawla A., Pollard J.W.: Macrophage biology in development,homeostasis and disease. Nature, 2013; 496: 445-455
  Google Scholar
• 45. Yeung J.H., Chan S.L., Or P.M.: Polysaccharide peptides from COV- 1 strain of Coriolus versicolor inhibit tolbutamide 4-hydroxylation inthe rat in vitro and in vivo. Food Chem. Toxicol., 2006; 44: 1414-1423
  Google Scholar
• 46. Yeung J.H., Or P.M.: Effects of polysaccharide peptides from COV- 1 strain of Coriolus versicolor on glutathione and glutathione-relatedenzymes in the mouse. Food Chem. Toxicol., 2007; 45: 953-961
  Google Scholar
• 47. Yu Z.T., Liu B., Mukherjee P., Newburg D.S.: Trametes versicolorextract modifies human fecal microbiota composition in vitro. PlantFoods Hum. Nutr., 2013; 68: 107-112
  Google Scholar
• 48. Ze Z.B., Li C.W., Han C.Y., Huo G.B.: Polysaccharopeptide researchprogress. Shandong Yiyao Gongye, 2003; 23: 30-31
  Google Scholar
• 49. Zhou X., Jiang H., Lin J., Tang K.: Cytotoxic activities of Coriolusversicolor (Yunzhi) extracts on human liver cancer and breast cancercell line. Afr. J. Biotechnol., 2007; 6: 1740-1743
  Google Scholar

Full text