Journal of Natural Medicines

, Volume 63, Issue 1, pp 32–40 | Cite as

In vivo growth-inhibition of Sarcoma 180 by an α-(1 → 4)-glucan–β-(1 → 6)-glucan-protein complex polysaccharide obtained from Agaricus blazei Murill

  • Maria Leônia Costa Gonzaga
  • Daniel Pereira Bezerra
  • Ana Paula Negreiros Nunes Alves
  • Nylane Maria Nunes de Alencar
  • Rodney de Oliveira Mesquita
  • Michael Will Lima
  • Sandra de Aguiar Soares
  • Cláudia Pessoa
  • Manoel Odorico de Moraes
  • Letícia Veras Costa-Lotufo
Original Paper


Agaricus blazei Murrill, a native mushroom of Brazil, has been widely consumed in different parts of the world due to its anticancer potential. This effect is generally attributed to its polysaccharides; however, the precise structure of these has not been fully characterized. To better understand the relationship between polysaccharide structures and antitumor activity, we investigated the effect of the intraperitoneally (i.p.) or orally (p.o.) administered α-(1 → 4)-glucan–β-(1 → 6)-glucan-protein complex polysaccharide from A. blazei alone or in association with 5-fluorouracil (5-FU) in tumor growth using Sarcoma 180 transplanted mice. Hematological, biochemical, and histopathological analyses were performed in order to evaluate the toxicological aspects of the polysaccharide treatment. The polysaccharide had no direct cytotoxic action on tumor cells in vitro. However, the polysaccharide showed strong in vivo antitumor effect. Thus, the tumor growth-inhibitory effect of the polysaccharide is apparently due to host-mediated mechanisms. The histopathological analysis suggests that the liver and the kidney were not affected by polysaccharide treatment. Neither enzymatic activity of transaminases (AST and ALT) nor urea levels were significantly altered. In hematological analysis, leucopeny was observed after 5-FU treatment, but this effect was prevented when the treatment was associated with the polysaccharide. In conclusion, this polysaccharide probably could explain the ethnopharmacological use of this mushroom in the treatment of cancer.


Agaricus blazei α-(1 → 4)-glucan–β-(1 → 6)-glucan-protein complex polysaccharide Antitumor activity Sarcoma 180 Toxicity 





Alanine aminotransferase


Aspartate aminotransferase


Colégio Brasileiro de Experimentação Animal, Brazil


Fourier transform infra red


Intraperitoneal route


3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide


Nuclear magnetic resonance


Natural killer


Oral route



We thank CNPq, Instituto Claude Bernard, FUNCAP, Banco do Nordeste and FINEP for the financial support in the form of grants and fellowship awards. The authors also thank the National Cancer Institute (Bethesda, MD, USA) for the donation of the tumor cell lines used in this study. The authors thank Silvana França dos Santos, Luciana França, and Maria de Fátima Teixeira for technical assistance.


  1. 1.
    Reen RK, Singh J (1991) In vitro and in vivo inhibition of pulmonary cytochrome P450 activities by piperine. J Exp Biol 29:568–573Google Scholar
  2. 2.
    Annu K, Neelima T, Usha Z, Bedi KL (1998) Piperine modulation of carcinogen induced oxidative stress in intestinal mucosa. Mol Cell Biochem 189:113–118CrossRefGoogle Scholar
  3. 3.
    Borchers AT, Keen CL, Gershwin ME (2004) Mushrooms, tumors, and immunity: an update. Exp Biol Med 229:393–406Google Scholar
  4. 4.
    Kawagishi H, Nomura A, Yumen T, Mizuno T, Hagiwara T, Nakamura T (1988) Isolation and properties of a lectin from the fruiting bodies of Agaricus blazei. Carbohydr Res 183:150–154PubMedCrossRefGoogle Scholar
  5. 5.
    Kimura Y, Kido T, Takaku T, Sumiyoshi M, Baba K (2004) Isolation of an anti-angiogenic substance from Agaricus blazei Murill: its antitumor and antimetastatic actions. Cancer Sci 95:758–764PubMedCrossRefGoogle Scholar
  6. 6.
    Gonzaga MLC, Ricardo NMPS, Heatley F, Soares SA (2005) Isolation and characterization of polysaccharides from Agaricus blazei Murill. Carbohydr Polym 60:43–49CrossRefGoogle Scholar
  7. 7.
    Kawagishi H, Inagaki R, Kanao T, Mizuno T, Shimura K, Ito H, Hagiwara T, Nakamura T (1989) Fractionation and antitumor activity of the water-insoluble residue of Agaricus blazei fruiting bodies. Carbohydr Res 186:267–273PubMedCrossRefGoogle Scholar
  8. 8.
    Kawagishi H, Kanao T, Inagaki R, Mizuno T, Shimura K, Ito H, Hagiwara T, Nakamura T (1990) Formolysis of a potent antitumor (1 → 6)-β-d-glucan-protein complex from Agaricus blazei fruiting bodies and antitumor activity of the resulting products. Carbohydr Polym 12:393–403CrossRefGoogle Scholar
  9. 9.
    Ohno N, Furukawa M, Miura NN, Adachi Y, Motoi M, Yadomae T (2001) Antitumor β-glucan from the cultured fruit body of Agaricus blazei. Biol Pharm Bull 24:820–828PubMedCrossRefGoogle Scholar
  10. 10.
    Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 16:55–63CrossRefGoogle Scholar
  11. 11.
    Bezerra DP, Castro FO, Alves APNN, Pessoa C, Moraes MO, Silveira ER, Lima MAS, Elmiro FJM, Costa-Lotufo LV (2006) In vivo growth-inhibition of Sarcoma 180 by piplartine and piperine, two alkaloid amides from Piper. Braz J Med Biol Res 39:801–807PubMedCrossRefGoogle Scholar
  12. 12.
    Bezerra DP, Castro FO, Alves APNN, Pessoa C, Moraes MO, Silveira ER, Lima MAS, Elmiro FJM, Alencar NMN, Mesquita RO, Lima MW, Costa-Lotufo LV (2008) In vitro and in vivo antitumor effect of 5-FU combined with piplartine and piperine. J Appl Toxicol 28:156–163PubMedCrossRefGoogle Scholar
  13. 13.
    Sousa APA, Torres MR, Pessoa C, Moraes MO, Rocha-Filho FD, Alves APNN, Costa-Lotufo LV (2007) In vivo growth-inhibition of Sarcoma 180 tumor by alginates from brown seaweed Sargassum vulgare. Carbohydr Polym 69:7–13CrossRefGoogle Scholar
  14. 14.
    Magalhes HIF, Veras ML, Torres MR, Alves APNN, Pessoa ODI, Silveira ER, Costa-Lotufo LV, Moraes MO, Pessoa C (2006) In vitro and in vivo antitumor activity of physalin B and D from Physalis angulata. J Pharm Pharmacol 58:235–241CrossRefGoogle Scholar
  15. 15.
    Lee YL, Kim HJ, Lee MS, Kim JM, Han JS, Hong EK, Kwon MS, Lee MJ (2003) Oral administration of Agaricus blazei (H1 strain) inhibited tumor growth in a Sarcoma 180 inoculation model. Exp Anim 52:371–375PubMedCrossRefGoogle Scholar
  16. 16.
    Liu JJ, Huang TS, Hsu ML, Chen CC, Lin WS, Lu FJ, Chang WH (2004) Antitumor effects of the partially purified polysaccharides from Antrodia camphorata and the mechanism of its action. Toxicol Appl Pharmacol 201:186–193PubMedCrossRefGoogle Scholar
  17. 17.
    Benet LZ, Kroetz DL, Sheiner LB (1996) Pharmacokinetics. The dynamics of drug absorption, distribution and elimination. In: Hardman JG, Limbird LE, Molini PB, Ruddon VRW, Gilman AG (eds) Goodman and Gilman’s The pharmacological basis of therapeutics. McGraw-Hill, New York, pp 3–28Google Scholar
  18. 18.
    Gebbia V, Puozzo C (2005) Oral versus intravenous vinorelbine: clinical safety proWle. Expert Opin Drug Saf 4:915–928PubMedCrossRefGoogle Scholar
  19. 19.
    Morinaga Y, Suga Y, Ehara S, Harada K, Nihei Y, Suzuki M (2003) Combination effect of AC-7700, a novel combretastatin A-4 derivative, and cisplatin against murine and human tumors in vivo. Cancer Sci 94:200–204PubMedCrossRefGoogle Scholar
  20. 20.
    Fujimiya Y, Suzuki Y, Oshiman K, Kobori H, Moriguchi K, Nakashima H, Matumoto Y, Takahara S, Ebina T, Katakura R (1998) Selective tumoricidal effect of soluble proteoglucan extracted from the basidiomycete, Agaricus blazei Murill, mediated via natural killer cell activation and apoptosis. Cancer Immunol Immunother 46:147–159PubMedCrossRefGoogle Scholar
  21. 21.
    Kobayashi H, Yoshida R, Kanada Y, Fukuda Y, Yagyu T, Inagaki K, Kondo T, Kurita N, Suzuki M, Kanayama N, Terao T (2005) Suppressing effects of daily oral supplementation of β-glucan extracted from Agaricus blazei Murill on spontaneous and peritoneal disseminated metastasis in mouse model. J Cancer Res Clin Oncol 131:527–538PubMedCrossRefGoogle Scholar
  22. 22.
    Ohno N, Hayashi M, Iino K, Suzuki I, Oikawa S, Sato K, Suzuki Y, Yadomae T (1986) Effect of glucans on the antitumor activity of grifolan. Chem Pharm Bull 34:2149–2154PubMedGoogle Scholar
  23. 23.
    Mizuno T, Hagiwara T, Nakamura T, Ito H, Shimura K, Sumiya T, Asakura A (1990) Antitumor activity and some properties of water-insoluble hetero-glycans from “Himematsutake”, the fruiting body of Agaricus blazei Murill. Agric Biol Chem 54:2889–2896Google Scholar
  24. 24.
    Mizuno M, Minato K, Ito H, Kawade M, Terai H, Tsuchida H (1999) Antitumor polysaccharide from the mycelium of liquid-cultured Agaricus blazei mill. Biochem Mol Biol Int 47:707–714PubMedGoogle Scholar
  25. 25.
    Itoh H, Ito H, Amano H, Noda H (1994) Inhibitory action of a (1 → 6)-beta-D-glucan-protein complex (F III-2-b) isolated from Agaricus blazei Murill (“himematsutake”) on Meth A fibrosarcoma-bearing mice and its antitumor mechanism. Jpn J Pharmacol 66:265–271PubMedCrossRefGoogle Scholar
  26. 26.
    Ebina T, Fujimiya Y (1998) Antitumor effect of a peptide-glucan preparation extracted from Agaricus blazei in a double-grafted tumor system in mice. Biotherapy 11:259–265PubMedCrossRefGoogle Scholar
  27. 27.
    Mizuno M, Morimoto M, Minato K, Tsuchida H (1998) Polysaccharides from Agaricus blazei stimulate lymphocyte T-cell subsets in mice. Biosci Biotechnol Biochem 62:434–437PubMedCrossRefGoogle Scholar
  28. 28.
    Kummar V, Abbas A, Fausto N (2004) Robbins and Cotran pathologic basis of disease. W.B. Saunders, ChinaGoogle Scholar
  29. 29.
    Scheuer PJ, Lefkowitch JH (2000) Drugs and toxins. In: Scheuer PJ, Lefkowitch JH (eds) Liver biopsy interpretation. W.B. Saunders, London, pp 134–150Google Scholar
  30. 30.
    McGee JOD, Isaacson PA, Wright NA (1992) Oxford textbook of pathology: pathology of systems. Oxford University Press, New YorkGoogle Scholar
  31. 31.
    Takiguchi N, Saito N, Nunomura M, Kouda K, Oda K, Furuyama N, Nakajima N (2001) Use of 5-FU plus hyperbaric oxygen for treating malignant tumors: evaluation of antitumor effect and measurement of 5-FU in individual organs. Cancer Chemother Pharmacol 47:11–14PubMedCrossRefGoogle Scholar

Copyright information

© The Japanese Society of Pharmacognosy and Springer 2008

Authors and Affiliations

  • Maria Leônia Costa Gonzaga
    • 3
  • Daniel Pereira Bezerra
    • 1
  • Ana Paula Negreiros Nunes Alves
    • 2
  • Nylane Maria Nunes de Alencar
    • 1
  • Rodney de Oliveira Mesquita
    • 1
  • Michael Will Lima
    • 1
  • Sandra de Aguiar Soares
    • 3
  • Cláudia Pessoa
    • 1
  • Manoel Odorico de Moraes
    • 1
  • Letícia Veras Costa-Lotufo
    • 1
  1. 1.Department of Physiology and Pharmacology, School of MedicineFederal University of Ceará, UFCFortalezaBrazil
  2. 2.Department of Clinical OdontologyFederal University of CearáFortalezaBrazil
  3. 3.Department of Organic and Inorganic ChemistryFederal University of CearáFortalezaBrazil

Personalised recommendations