Antitumor .BETA.-Glucan from the Cultured Fruit Body of Agaricus blazei.

Abstract

An immunomodulating substance, a biological response modifier (BRM) or biotherapy is important for the treatment of cancer and infectious diseases. b-Glucan is a well-known BRM which is widely distributed in nature and used as a medicine and food. [1][2][3][4][5] The effects of "Lentinan" from Lentinus edodes and "Sonifilan" (SPG) from Schizophyllum commune in cancer therapy have been clinically proven.6,7) We have already developed b-glucans, GRN from Grifola frondosa, [8][9][10] SSG and TSG from Sclerotinia sclerotiorum, [11][12][13] OL-2 from Omphalia lapidescens, 14) PVS and PVG from Peziza vesiculosa, 15) CSBG from Candida spp., 16) OX-ZYM from a yeast cell preparation, zymosan, 17,18) and SCG from Sparaccis crispa. 19) We have also prepared several carboxymethyl, hydroxyethyl, sulfate, and polyol derivatives of the above b-glucans.20) In addition, we have analyzed the mechanism of b-glucan mediated immunopharmacological activity and identified the conformation dependent and independent activity. [21][22][23][24][25] These rather complicated relationships between structure and activity suggest the contribution of multiple receptor-ligand interactions in b-glucan mediated immunopotentiation.The incidence of cancer is gradually increasing and the spectrum of cancer-prone organs is changing each year. In addition to surgery, irradiation, and chemotherapy, immunotherapy is believed to be an important cancer therapy. 26)Immunotherapy and biotherapy include various approaches, such as BRMs, cytokines, lymphocyte transplantation, gene therapy, and herbal and alternative medicines. Clinical trials of these therapies are being widely carried out, and clinical evidence suggests their efficacy, although the precise mechanisms are still difficult to understand. The development of additional b-glucans is still needed for better biotherapy and to understand the molecular mechanisms.Agaricus blazei is a medical mushroom widely eaten and prescribed in Japan. There are various kind of health foods containing A. blazei and/or its extracts, but the molecular mechanisms of its action is far beyond complete understanding. The most anticipated pharmacological effect of A. blazei is modulation of the immune system against cancer. In the last decade, there have been several studies which focused on an antitumor polysaccharide from A. blazei, i.e., 1,6-b-glucan, glucan-protein complex, a-glucan, and heteroglycan. 27-34) Antitumor polysaccharides were screened not only in the fruitbody but also the liquid cultured medium and mycelium. One of the best characterized components, FIII-2-b, was prepared from the sodium hydroxide extract of the fruit body, and the structure was analyzed by methylation and NMR analyses. Contribution of a protein moiety to the activity of FIII-2-b was speculated by loss of the activity by partial formolysis. In the preliminary investigation, we have also determined that the major carbohydrate component of the fruit body of A. blazei is 1,6-b-glucan; however, we have already shown that a linear 1,6-b-glucan,...

Stimulation of human monocytic cells by the medicinal mushroom Agaricus blazei Murill induces expression of cell surface markers associated with activation and antigen presentation

“…Spores of AbM were taken to Japan in the mid-60s for commercial cultivation and research. AbM is rich in antitumor protein-glucan complexes [17], and β-glucans [18], which are potent stimulators of macrophages [19,20], granulocytes [21], natural killer (NK) cells [22] and DC [23]. The immunomodulatory properties and health effects of AbM have recently been reviewed [24].…”

Proteoglycans Regulate the Chemotaxis of Dendritic Cells Derived from Human Peripheral Blood Monocytes

“…6) The major carbohydrate component of the fruit body of Agaricus blazei is b-glucan (mainly 1,6-b-glucan) 25) and PGs purified from the Agaricus blazei could induce maturation of DCs derived from murine bone marrow. 8) These findings indicate that the smaller molecules such as polysaccharides and GAGs may be able to better activate the immune response than enormous molecules such as PG in the maturation of DCs.…”

Effects of different extracts of the mushroom Agaricus blazei Murill on the hematologic profile of mice with Ehrlich tumor

“…Agaricus subrufescens Peck, Agaricus brasiliensis, according to Wasser et al (2002), commonly known as the sun mushroom, is marketed fresh for consumption and in syrups, solutions, and capsules in Brazil (ANVISA, 2003). Substances extracted from this mushroom, including 1.6-beta-glucan, 1.3-betaglucan, active hemi-cellulose compounds, and anti-tumor organic substance Mie, aid the treatment of neoplasm by increasing the number and activity of natural killer (NK) cells and titration of immunoglobulins (IgM, IgG) and Interleukin-1 (Itho et al, 1997;Ohno et al, 2001;Takeshi et al, 2001;Gennari et al, 2002;Oshiman et al, 2002). Methanolic extracts of immature and mature ABM, although differing in concentrations of phenolic compounds, show similar antioxidant activity, except for the chelating capacity of ferrous ions, which is greater in the cups of ripe fruit (Soares et al, 2009).…”