Antitumor effect of a peptide-glucan preparation extracted from Agaricus blazei in a double-grafted tumor system in mice
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The antitumor effect of extracts obtained from the fruit body of Agaricus blazei Murill was examined in a double-grafted tumor system, in which BALB/ c mice received simultaneous intradermal injections of Meth-A tumor cells in both the right (106 cells) and left flank (2 × 105 cells), and were then injected with 5 mg of extracts of A. blazei in the right tumor on days 3, 4 and 5. Intratumoral administration of ethanol-soluble (Fraction 1), water-ethanol-soluble (Fraction 2), ammonium oxalate-soluble (Fraction 3) and ammonium oxalate-insoluble (Fraction 4) fractions resulted in inhibition of tumor growth, with Fraction 3 showing the most tumoricidal activity, producing regression of the right tumor and inhibitition of growth of the left, non-injected tumor. The maximum effect was obtained using 0.5 mg of Fraction 3 and this amount was used in subsequent experiments. The antitumor effect of intratumorally administered Fraction 3 was enhanced by oral ad lib administration of feed containing 0.083% of Fraction 3. When immunized spleen cells from mice that had been cured by intratumoral administration of 0.5 mg of Fraction 3 were directly injected (2 × 107 cells/mouse) into the Meth-A tumor, tumor growth was inhibited. The tumor cells on day 7 from the Fraction 3-treated right tumor and from the left tumor were cultured for 24 h and their culture supernatants were assayed for neutrophil or macrophage chemotactic activity. Significant macrophage chemotactic factor activity was detected in the culture media from the left tumor tissue. Serum levels of immunosuppressive acidic protein (IAP), produced by activated macrophages and neutrophils, increased transiently soon after intradermal injection of 0.5 mg of Fraction 3. These results suggest that regression of the left non-injected tumor was due to an immune reaction, involving induction of cytotoxic cells in the spleen, and the release of chemotactic factors in the distant tumor.
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- 1.Fujimiya Y, Suzuki Y, Oshima K, Kobori H, Moriguchi K, Nakashima H, Matsumoto Y, Takahara 5, Ebina T and Katakura R. Selective tumoricidal effect of soluble proteoglu-can extracted from the basidiomycete, Agaricus blazeiMurill, mediated via natural killer cell activation and apoptosis. Can-cer Immunology & Immunotherapy 1998; 46: 135–147.Google Scholar
- 2.Ebina T, Kohya H, Yamaguchi T and Ishida N. Antimetasta-tic effect of biological response modifiers in the 'double-graftedtumor system'. Jpn. J. Cancer Res. 1986; 77: 1034–1042.Google Scholar
- 3.Ebina T and Kohya H. Antitumor effector mechanism at a distant site in the double-graftedtumor system of PSK, a protein-bound polysaccharide preparation. Jpn. J. Cancer Res. 1988; 79: 957–964.Google Scholar
- 4.Ebina T, Kohya H and Ishikawa K. Antitumor effect of PSK: Role of regional lymph nodes and enhancement of concomi-tant and sinecomitant immunity in the mouse. Jpn. J. Cancer Res. 1989; 80: 158–166.Google Scholar
- 5.Kohya, H., Ebina, T., Yamaguchi, T. and Ishida, N. The 'double-grafted tumor system' proposed to find effector cells in the analyses of antitumor effect of BRMs. Biotherapy 1989; 1: 139–151.Google Scholar
- 6.Ebina T and Murata K. Antitumor effect of PSK at a distant site: Inductions of interleukin-8-like factor and macrophage chemotactic factor in murine tumor. Jpn. J. Cancer Res 1990; 81: 1307–1313.Google Scholar
- 7.Ishikawa K, Majima T and Ebina T. Antitumor effect of a Col-iolus preparation, PSK: induction of macrophage chemotactic factor (MCF) in spleens of tumor bearing mice. Biotherapy 1992; 5: 251–258.Google Scholar
- 8.Ebina T, Murata K and Tamura K. Antitumor effect of in-tratumoral administration of biological response modiifiers: Induction of immunosuppressive acidic protein, a type of α1-acid glycoprotein, in mice. Jpn. J. Cancer Res. 1994; 85: 93–100.Google Scholar
- 9.Shibata Y., Tamura K. and Ishida N. In vivo analysis of the suppressive effects of immunosuppressive acidic protein, a type of α1 acid glycoprotein, in connection with its high level in tumor-bearing mice. Cancer Res. 1983; 43: 2889–2896.Google Scholar
- 10.Ishida N, Shibata Y and Tamura K. Serum protein factors against self-defense which are activated in cancer patients. In 'Self-Defense Mechanisms, Role of Macrophages,' ed. D Mizuno, Z A Cohn, K Takeya and N Ishida, Tokyo, University of Tokyo Press, 1982}, 239–2Google Scholar
- 11.Dubois M, Gilles KA, Hamilton JK, Rebers PA and Smith F. Colorimetric method for determination of sugars and related substances. Anal. Chem. 1956; 28: 350–356.Google Scholar
- 12.Lowry OH, Rosebrough NJ, Farr AL and Randall RJ. Protein measurement with the folin phenol reagent. J. Biol. Chem. 1951; 193: 265–275.Google Scholar