Cancer Immunology, Immunotherapy

, Volume 46, Issue 3, pp 147–159

Selective tumoricidal effect of soluble proteoglucan extracted from the basidiomycete, Agaricus blazei Murill, mediated via natural killer cell activation and apoptosis

  • Yoshiaki Fujimiya
  • Youichi Suzuki
  • Ko-ichi Oshiman
  • Hidekazu Kobori
  • Koichi Moriguchi
  • Hisako Nakashima
  • Yonezo Matumoto
  • Shogo Takahara
  • Takusaburo Ebina
  • Ryuichi Katakura
ORIGINAL ARTICLE

DOI: 10.1007/s002620050473

Cite this article as:
Fujimiya, Y., Suzuki, Y., Oshiman, K. et al. Cancer Immunol Immunother (1998) 46: 147. doi:10.1007/s002620050473

Abstract

 We have isolated a novel type of natural tumoricidal product from the basidiomycete strain, Agaricus blazei Murill. Using the double-grafted tumor system in Balb/c mice, treatment of the primary tumor with an acid-treated fraction (ATF) obtained from the fruit bodies resulted in infiltration of the distant tumor by natural killer (NK) cells with marked tumoricidal activity. As shown by electrophoresis and DNA fragmentation assay, the ATF also directly inhibited tumor cell growth in vitro by inducing apoptotic processing; this apoptotic effect was also demonstrated by increased expression of the Apo2.7 antigen on the mitochondrial membranes of tumor cells, as shown by flow-cytometric analysis. The ATF had no effect on normal mouse splenic or interleukin-2-treated splenic mononuclear cells, indicating that it is selectively cytotoxic for the tumor cells. Cell-cycle analysis demonstrated that ATF induced the loss of S phase in MethA tumor cells, but did not affect normal splenic mononuclear cells, which were mainly in the G0G1 phase. Various chromatofocussing purification steps and NMR analysis showed the tumoricidal activity to be chiefly present in fractions containing (1→4)-α-D-glucan and (1→6)-β-D-glucan, present in a ratio of approximately 1:2 in the ATF (molecular mass 170 kDa), while the final purified fraction, HM3-G (molecular mass 380 kDa), with the highest tumoricidal activity, consisted of more than 90% glucose, the main component being (1→4)-α-D-glucan with (1→6)-β branching, in the ratio of approximately 4:1.

Key words AgaricusNatural killer cellsα-GlucanApoptosis

Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • Yoshiaki Fujimiya
    • 1
  • Youichi Suzuki
    • 2
  • Ko-ichi Oshiman
    • 3
  • Hidekazu Kobori
    • 3
  • Koichi Moriguchi
    • 4
  • Hisako Nakashima
    • 4
  • Yonezo Matumoto
    • 4
  • Shogo Takahara
    • 3
  • Takusaburo Ebina
    • 1
  • Ryuichi Katakura
    • 2
  1. 1.Division of Immunology, Miyagi Cancer Center Research Institute, Natori, Japan 9811293JP
  2. 2.Division of Neurosurgery, Miyagi Cancer Center Research Institute, Natori, Japan 9811293JP
  3. 3.Division of Biotechnology, Sumitomo Forestry Tsukuba Research Institute, Tsukuba, Ibaraki, Japan 3002646JP
  4. 4.Division of Scientific Instrument, Sumika Chemical Analysis Service, Inc., Osaka, Japan 5540022JP