Effects of D-Fraction, a Polysaccharide from Grifola frondosa on Tumor Growth Involve Activation of NK Cells.

Abstract

We previously reported that the (1®3)-branched (1®6)-bglucan termed D-Fraction, extracted from the fruit body of the maitake mushroom (Grifola frondosa) ( Fig. 1), is a biological response modifier (BRM) like lentinan, which is found in Letinus edodes. [1][2][3] These polysaccharides enhance the activity of immunocompetent cells such as macrophages, helper T cells, and cytotoxic T cells, which attack tumor cells. These effects of BRMs led us to hypothesize that oral administration of D-Fraction would be an effective treatment for cancer patients. Orally administered D-Fraction was shown to reduce tumor size in mice, without causing unwanted side effects.2) Therefore, D-Fraction has been commercialized as a health material, the safety of which has been confirmed by the Consumer Product Testing Co. (New Jersey, U.S.A.) We have already tried a non-randomized clinical trial of D-Fraction therapy for patients with lung and breast cancer in stages II-IV. 4) In this trial, we found that IL-2 production was enhanced in D-Fraction-treated patients, suggesting that macrophages and T cells were activated by DFraction. In addition, D-Fraction is revealed to be effective for human immunodeficiency virus (HIV) infection 5) and listeriosis, 6) by reinforcing the immune system. These results indicate that one network of the immuno-response pathway by which D-Fraction enhances anti-tumor effects is dependent on an adaptive immunity associated with cytotoxic T cell activation.Natural killer (NK) cells rapidly recognize and lyse a large variety of tumor or virus-infected cells, without the need for either prior sensitization or MHC-dependent recognition, which is different from cytotoxic T cell. 7) Pham-Nguyen et al. have reported that the early NK cell response alone is not sufficient for tumor clearance, and that both T cells and NK cells are required in the development of the long-term survival in the hepatic tumor model by IL-12-mediated gene therapy. 8) In our clinical study, we also found that D-Fraction activated NK cells in lung, breast and liver carcinoma patients for long periods of time, exceeding one year (Table 1) MATERIALS AND METHODS MaterialsFor the detection of human NK activity, chromium-51 (Daiichi Kagaku Yakuhin Co., Tokyo) and lymphopacel (dϭ1.077) (IBL Co., U.S.A.) were prepared.Animals Male C3H/HeN mice (4-weeks-old) were obtained (Japan Crea Co., Osaka) and were raised for one week before being used for experiments. Food and water were given freely to these mice until used for experiments.Cells MM-46 carcinoma cells were kindly donated by Dr. Kanki Komiyama. 51Cr labeled K-562 cells were used as target cells of human NK.Preparation of D-Fraction D-Fraction was prepared from the dried powder of the fruit body of maitake mushrooms (Grifola frondosa) (Yukiguni Maitake Co., Niigata), according to the method described in our previous paper. 6)The level of LPS contained in D-Fraction was determined by using Endospecy ES-20S Set (Seikagaku Industry Co., Tokyo), and the ratio (%) of LPS in D-Fraction was less than...

Effects ofGrifola frondosanon-polar bioactive components on high-fat diet fed and streptozotocin-induced hyperglycemic mice

“…Regular consumption of GF is believed to enhance immune systems, to lower blood glucose, and to improve the spleen, stomach, and nerve functions. Extracts and polysaccharides of liquid cultured GF have been shown to possess immunomodulatory (Kodama et al, 2004), anticarcinogenic (Kodama et al, 2002), antihyperglycemic (Horio & Ohtsuru, 2001;Kubo et al, 1994;Manohar et al, 2002), antihypertensive , antihyperlipidemic (Fukushima et al, 2001), and antioxidative (Zhang et al, 2002) activities. a-Glucan of GF fruiting bodies was demonstrated to have antidiabetic activity in type 2 diabetic animals (Lei et al, 2007).…”

Effects of Ligustilide on Tumor Growth and Immune Function in Institute of Cancer Research Mice

“…T cells can kill tumors and produce many lymphocyte factors consisting of macrophage mobile factor, lymphotoxin, transfer factor and interferon, which can enhance macrophage phagocytosis and the capacity of killing target cells [21]. NK cells mediate the immediate killing of tumor cells and play a primary role in regulating immune responses as well [22].…”

Therapeutic mechanism of ginkgo biloba exocarp polysaccharides on gastric cancer

“…The sugar-chain of polysaccharides can regulate cell proliferation, differentiation, growth and aging. They showed definite therapeutic effectiveness in anti-tumor therapy, and the ability to enhance body's immune function, as well as a lower toxic side-effect [7][8][9][10] . For example, mushroom polysaccharides have already been used as a drug to regulate the organism reaction in clinical therapy and to prevent tumors in Japan.…”