Orally Administered β-1,6-D-Polyglucose Extracted from Agaricus blazei Results in Tumor Regression in Tumor-Bearing Mice

Abstract

There is an increasing demand from both patients and practicing oncologists for orally formulated chemotherapy. The present study focused on the oral formulation for natural products that may be effectively used in oncologic treatment regimens. Tumor-bearing mice treated with intratumoral administration of aqueous ammonium oxalate-soluble and ethanol-insoluble derivatives of Agaricus blazei showed marked tumor regression at doses ranging from 0.1 to 2.5 mg (p < 0.05 vs. saline control; n = 7). However, oral administration of this same fraction, either prior to, simultaneously with, or after, tumor cell inoculation did not result in tumor regression (p > 0.05 vs. control). When this fraction was treated with hydrochloric acid (acid-treated fraction; ATF), intratumoral administration resulted in a marked regression of tumor growth comparable to that of the acid-untreated fraction. More importantly, parenteral administration of ATF resulted in a significantly greater regression of tumor growth than that produced by the untreated fraction (p < 0.05 vs. untreated; n = 7). When a total of 4.5 mg of ATF was given orally at varying schedules prior to, simultaneously with, or after, tumor inoculation, a significant regression was seen using a schedule starting 4 days prior to inoculation (p < 0.05 vs. all other treatments; n = 7). NMR and molecular analyses showed that the ATF fraction had a molecular weight of approximately 10 kDa and consisted mainly of only (1,6)-beta- D-polyglucose. These results suggest that the oral administration of simple acid-treated ATF results in a remarkable tumor regression. Thus, simple acid hydrolysis of natural products may not only bring measurable benefits in oncological practice, but may also be a useful general formulation for natural products for oral chemotherapy.

Bcl-2 and Caspase-3 Are Major Regulators in Agaricus blazei-Induced Human Leukemic U937 Cell Apoptosis through Dephoshorylation of Akt

“…Cell Viability Test The cells were seeded at a density of 5ϫ10 5 cell/ml and then incubated under various conditions as specified in the text. MTT (0.5 mg/ml) was subsequently added to each well.…”

Toward a Core Nutraceutical Program for Cancer Management

“…A number of polysaccharide-rich preparations derived from various types of mushrooms-some of which have long been used in folk medicine-have been studied with respect to their ability to act as orally effective immunostimulants; preparations derived from Agaricus blazei Murr (Agaricaceae; Brazilian sun mushroom), Ganoderma lucidum P Karst (Ganodermataceae; reishi), and Lentinula (Lentinus) edodes (Berk) Pegler (Marasmiaceae; shiitake), among others, have shown potential in this regard. [66][67][68][69][70][71][72][73][74][75][76][77][78] The polysaccharides derived from Agaricus and Ganoderma mycelia-β-Dglucans with 1 → 3 and 1 → 6 linkages-have been shown to activate macrophages via toll-like receptor 4 and CD14 (the receptor system activated by lipopolysaccharides). [79][80][81] The oral efficacy of some preparations of these polysaccharides evidently reflects the fact that these are at least partially absorbable despite their high molecular weight (usually in excess of 10 kD).…”

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

“…The polysaccharide content was affected by the extraction method, and this is relevant, since β-glucan in ABM has been shown to modulate the immune system (Oshiman et al, 2002).…”

“…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).…”