on Anti-tumor /Immune Activating Activities

( a complete paper may be available upon request)

1) Antitumor activity of orally administered "D-fraction" from Maitake mushroom (Grifola frondosa)
Journal of Naturopathic Medicine, 1993, Vol. 4, No. 1, P.10-15

It is well-known in Japan that some medicinal mushrooms contain polysaccharide compounds which demonstrate antitumor activity. The author obtained the acid-insoluble, alkali-soluble, hot-water extractable polysaccharide (containing about 30% of protein) "D-fraction" from the fruiting body of the Maitake mushroom which exhibited antitumor activity against allogenic and syngeneic tumors on oral administration to mice. A Winn assay revealed a complete tumor inhibition indicating that stimulation of an immune response triggered by the tumor-bearing state is activated by D-fraction. The cytolytic activity and interleukin-1 productivity of macrophages or T cells which exhibit antigen-specific cytotoxicity were enhanced. Footpad swelling test against D-mice (D-fraction administered tumor-bearing mice) suggested that delayed type hypersensitivity (DTH) reaction against tumor antigen was potentiated. Winn assay was carried out with whole spleen cells from D-mice and Lyt-2 spleen cells in which Lyt-2 cells corresponding to cytotoxic T cells (CTL) were eliminated by treating with anti-Lyt-2 monoclonal antibody and complement. It confirmed that tumor neutralizing activity was at no time impaired even after CTL were eliminated, concluding that a DTH reaction, manifested by the combined action of delayed hypersensitivity T cells (T dh) and macrophages was potentiated by oral administration of D-fraction.

2) Activity of Maitake D-fraction to Inhibit Carcinogenesis and Metastasis
Annals of the New York Academy of Sciences, Volume 768, September 30, 1995, P.243-245

The author has been involved in research on medicinal properties of edible mushrooms for the last 15 years and have reported that, of all medicinal mushrooms studied, Maitake mushroom (Grifola frondosa) has the strongest antitumor activity in tumor growth inhibition both when administered orally and intraperitoneally. In fact, most of the other mushroom extracts are reported ineffective when given orally. In this report, the author has investigated Maitake's activities on the inhibition of carcinogenesis and formation of the secondary focus due to the metastasis of tumor cells in lymph and blood.

3) Maitake, Grifola frondosa: Pharmacological Effects
Food Reviews International, 11(1), P.135-149 (1995)

There are three homologs of Maitake, Grifola frondosa: Shiromaitake, Grifola albicans; choreimaitake, Grifola umbellata; and Tonbimaitake, Grifola gigantea. Maitake grows in the northern part of the Temperate Zone in the Northern Hemisphere and is found throughout Japan, Europe, and North America.

Wild Maitake can be harvested in September/October. It forms large heads, mainly near the roots of big fagaceous trees such as Mizunara, Quercus crispula, Buna, Fagus crenata, and Shiinoki, Castanopsis cuspidata. It grows in Ume, Prunus ume; persimmon, Diospyros kaki; plum, Prunus salicina; apricot, Prunus armeniaca var. anzu; peach, Prunus persica var. vulgaris; and oak trees, Quercus serrata. It is one of the fungi which invades the core of these trees. It decomposes lignin and leaves and cellulose. It is the cause of so-called white rot. Wild Maitake has a good taste, a crisp texture, and an excellent aroma. It is considered a first-rank edible mushroom.

The scientific name of Maitake, "Grifola frondosa" comes from the common name of a fungus found in Italy. This name refers to a mythical beast which is half-lion and half-eagle. The Japanese name "Maitake" is associated with its shape, which some believe resembles a dancing nymph. It is also said that this name comes from "Dancing fungus", because the person who finds it dances with joy. Maitake is used as a Chinese medicine called "Keisho". "Shen Nong Ben Cao jing" (Shen Nong's scripture of herbal medicine) states that it has been frequently used for improving spleen and stomach ailments, calming nerves and mind, and treating hemorrhoids.

4) Potentiation of Host-Mediated Antitumor Activity in Mice by -Glucan Obtained from Grifola frondosa (Maitake)
Chem. Pharm. Bull. 35(1), P.262-270 (1987)

A polysaccharide (3-branched -1,6-glucan MT-2) extracted from fruite body of Grifola frondosa (maitake) showed an antitumor effect against mouse syngeneic tumors (MM-46 carcinoma and IMC-carcinoma). It is not only directly activates various effector cells (macrophages, natural killer cells, killer T cells, etc) to attack tumor cells, but also potentiates the activities of various mediators including lymphokines and interleukin-1. Thus, it acts to potentiate cellular functions and at the same time to prevent a decrease of immune functions of the tumor-bearing host.

5) Maitake D-fraction: Healing and Preventive Potential for Cancer
Journal of Orthomolecular Medicine, vol. 12, No. 1, First Quarter, 1997,

Author has been studying medicinal mushrooms for the last 15 years and has reported that of all mushrooms studied, Maitake Mushroom (Grifola frondosa) has the strongest activity in tumor growth inhibition both in administered orally and intraperitoneally. In this report, Maitake extract D-fraction was investigated to determine its effectiveness not only on the inhibition against tumors already growing, but also on the inhibition of formation of the secondary focus due to metastasis of tumor cells in lymph and /or blood. In the tests of cancer inhibition rates on mice bearing MM46 (breast cancer), they were bred for one month with foods containing 20% edible mushroom powder. The result was that Maitake outperformed all other mushrooms. Through the 31 day oral administration, total remission of the tumor was visibly confirmed on four out of ten Maitake fed mice. The remaining six rodents also indicated almost 90% suppression rate compared to untreated (control) mice. Most other mushroom extracts are reported ineffective when given orally. The results of human studies on Maitake D-fraction is reported which indicated strong potential of Maitake D-fraction for Cancer Nutrition.

6) Antitumor Activitiy and Immunological Property of Polysaccharides from the Mycelium of Liquid Cultured Grifola frondosa,
Journal of the Japanese Society for Food Science and Technology Vol.41, No. 10, P.724-732 (1994)

7) Effect of Maitake D-fraction on Cancer Prevention
Annals of the New York Academy of Science, Vol.833, Dec.29, 1997, P.204-207

It has been reported that the protein-bound beta-glucan (D-fraction) extracted Maitake mushroom has the ability to inhibit the tumor growth by oral administration as well as i.p. injection. Now we are investigating whether D-fraction is effective against chemically induced cancer and against metastasis or recrudenscence of MM-46 breast cancer. BALB/C mice were prepared and cancer-inducing 3-MCA was injected. On the 15th day 0.2mg of D-fraction was orally administered for 15 days. After 30 days, the number of mice with cancer was 30.7% in the experimental group and 93.2% in the control group, showing the anti-carcinogenic activity of D-fraction. MM-46 breast cancer was intraperitoneally implanted in C3H mice and the formed tumor surgically removed. Then 0.2mg of D-fraction was injected for 10 days. After 20 days, the tumor metastasis was inhibited by 92.1% in mice given D-fraction compared to the control group and tumor recrudescence was also inhibited by 91.9%. Also, the synergistic effect of Mitomycin C (widely used anti-cancer drug) and Maitake D-fraction was confirmed on cancer metastasis inhibition.

8) Antitumor Activity Exhibited by Orally Administered Extract from Fruit Body of Grifola frondosa (maitake)
. Pharm. Bull.36(5): P.1819-1827 (1988)

The acid-insoluble, alkali-soluble, hot-water-extractable polymer (a polysaccharide containing approximately 30% of protein; D-fraction) obtained from the fruit bodies of Grifola frondosa (maitake) exhibited antitumor activities against allogenic and syngeneic tumors on oral administration to mice. Winn assay conducted to examine the tumor growth-suppressing effect revealed a complete inhibition of the tumor by the oral administration of D-fraction. This fact indicates that stimulation of the immune response system triggered by the tumor-bearing state is activated by D-fraction. Consequently, the activity of D-fraction on cells associated with immune response was examined. The cytolitic activity and interleukin-1 productivity of macrophages or T cells which exhibit antigen-specific cytotoxicity were enhanced. D-fraction was found to potentiate the delayed-type hypersensitivility response which is associated with tumor growth suppression.

9) The Chemical Structure of an Antitumor Polysaccharide in Fruit Bodies of Grifola frondosa (maitake)
. Pharm. Bull.35(3):P.1162-1168 (1987)

A polysaccharide was extracted from fruit bodies of Grifola frondosa (maitake), and the chemical structure and antitumor activity were studied. The extracted polysaccharide could be hydrolyzed by -glucanase into glucose, indicating it to be a -glucan. The sample gave methyl 2,3,4,6-tetra--, methyl 2,4,6-tri--, methyl 2,3,4 -tri-- and metyhl 2,4 -di--methylglucoside in the molar ratio of 4:2:1:4 on methylation. In the carbon-13 nuclear magnetic resonance spectrum, the signals of C-6' (related to (1-6) bonding) and C-3' (related (1-3) bonding) were observed in addition to those of free C-6 and C-3. These results indicate that the major chain is made up of -1,6-linked glucose residues with branches of -1,3-linked glucose. This glucan inhibited the growth of Sarcoma 180 tumor in ICR mice.

10) Monoclonal antibody to proteoglycan derived from Grifola frondosa (maitake)
. Pharm. Bull. April. 1994; 17(4): P.539-542
Research Laboratory, Taito Co., Ltd., Kobe, Japan.

A murine monoclonal antibody (MAb) was prepared by immunizing BALB/c mice with a proteoglycan fraction derived from Grifola frondosa (Maitake mushroom), followed by the hybridization of spleen cells with mouse myeloma cells. The MAb (subclass; 1g G2b), designated MPG2, reacted with schizophyllan (SPG), curdlan, scleroglucan, laminarin and lentinan, but not with dextran, pullulan, mannan and xylan. Immunohistochemistry (ABC-GO method) showed that MAb MPG2 reacted with lysosomal proteoglycan and (1-->6)-beta-branched laminaritriose taken up by rabbit peritoneal macrophages. These results suggest that this MAb may recognize mainly (1-->3)-beta-D-glucan, and may be useful for determining the immunological properties of Grifola frondosa-derived proteoglycan.

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