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Journal of Cancer Research and Clinical Oncology

, Volume 131, Issue 8, pp 527–538 | Cite as

Suppressing effects of daily oral supplementation of beta-glucan extracted from Agaricus blazei Murill on spontaneous and peritoneal disseminated metastasis in mouse model

  • Hiroshi Kobayashi
  • Ryuji Yoshida
  • Yasufumi Kanada
  • Yoichi Fukuda
  • Tatsuo Yagyu
  • Kiyokazu Inagaki
  • Toshiharu Kondo
  • Noriyuki Kurita
  • Mika Suzuki
  • Naohiro Kanayama
  • Toshihiko Terao
Original Paper

Abstract

Purpose: The Basidiomycete fungus Agaricus blazei Murill has traditionally been used as a health food for the prevention of cancer. Methods: We examined whether beta-(1–6)-D-glucan extracted from A. blazei is a potential anticancer agent in an in vitro and in vivo animal model. Results: Here we show that (1) beta-glucan had cytotoxic effect against human ovarian cancer HRA cells, but not against murine Lewis lung cancer 3LL cells, in vitro; (2) beta-glucan promotes p38 MAPK activity for suppressing HRA cell proliferation and amplifying the apoptosis cascade; (3) beta-glucan stimulates translocation of the proapoptotic protein, Bax, from the cytosol to mitochondria, cytochrome c release, and subsequent caspase-9 activation; (4) treatment with SB203580, a p38 MAPK-specific inhibitor, suppresses beta-glucan-induced effects, indicating that activation of p38 MAPK is involved in the suppression of cell proliferation and mitochondrial activation-mediated cell death pathway; (5) in mice, oral supplementation with beta-glucan reduces pulmonary metastasis of 3LL cells and peritoneal disseminated metastasis of HRA cells and inhibits the growth of these metastatic tumors in lung or peritoneal cavity, in part, by suppressing uPA expression; and (6) in an in vivo experimental metastasis assay, however, the oral supplementation with beta-glucan after i.v. tumor cell inoculation did not reduce the number of lung tumor colonies. Conclusion: Treatment with beta-glucan may be beneficial for cancer patients with or at risk for metastasis. The beta-glucan-dependent signaling pathways are critical for our understanding of anticancer events and development of cancer therapeutic agents.

Keywords

Agaricus blazei Beta-glucan Metastasis Proliferation Urokinase 

Abbreviations

3LL

Murine Lewis lung carcinoma

MAPK

Mitogen-activated protein kinase

uPA

Urokinase-type plasminogen activator

FCS

Fetal calf serum

ERK

Extracellular signal-regulated kinase

JNK

c-Jun N-terminal kinase

TGF-β

Transforming growth factor-beta

Notes

Acknowledgements

Agaricus blazei was obtained from K. Naito (DreamWorld Co., Ltd.). This work was supported by a grant-in-aid for Scientific Research from the Ministry of Education, Science and Culture of Japan (to H.K.), by grants from the Fuji Foundation for Protein Research (H.K.), the Kanzawa Medical Foundation (H.K.), Sagawa Cancer Research foundation (H.K.), and Aichi Cancer Research foundation (H.K).

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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Hiroshi Kobayashi
    • 1
  • Ryuji Yoshida
    • 2
  • Yasufumi Kanada
    • 2
  • Yoichi Fukuda
    • 3
  • Tatsuo Yagyu
    • 4
  • Kiyokazu Inagaki
    • 4
  • Toshiharu Kondo
    • 5
  • Noriyuki Kurita
    • 6
  • Mika Suzuki
    • 1
  • Naohiro Kanayama
    • 1
  • Toshihiko Terao
    • 1
  1. 1.Department of Obstetrics and GynecologyHamamatsu University School of MedicineHamamatsu, ShizuokaJapan
  2. 2.Food Science Research Institute, Tsukuba R&D CenterFuji Oil Co LtdTsukuba-gun, IbarakiJapan
  3. 3.Hannan R&D CenterFuji Oil Co LtdIzumisano, OsakaJapan
  4. 4.NetForce Co LtdNagoya, AichiJapan
  5. 5.Computer Technology Integration (CTI) Co LtdNagoya, AichiJapan
  6. 6.Department of Knowledge-Based Information EngineeringToyohashi University of TechnologyTempaku-cho, ToyohashiJapan

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