Antitumor Activity and Hematopoietic Response of a b-Glucan Extracted from an Edible and Medicinal Mushroom Sparassis crispa Wulf.: Fr. (Aphyllophoromycetideae)

Ohno, Naohito; Harada, Toshie; Masuzawa, Shinya; Miura, Noriko N.; Adachi, Yoshiyuki; Nakajima, Mitsuhiro; Yadomae, Toshiro

doi:10.1615/intjmedmushr.v4.i1.20

Cited by 28 publications

(26 citation statements)

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“…administration of SCG enhanced the hematopoietic response in CY-induced leukopenic mice from a qualitative as well as quantitative point of view. 12,13) In this study, we show that the combination of IFA and SCG provides hematopoietic responses that are synergistically enhanced over isoflavone or b-glucan alone. …”

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confidence: 63%

“…Both oral and intraperitoneal administration of SCG modulated the recovery rate of each population, and recovered such populations in the peritoneal cavity, liver, spleen and bone marrow (BM) faster than in the control group. 12,13) On the other hand, recent studies have suggested that soy isoflavones have a suppressive effect on some macrophage functions, such as platelet aggregation, inflammation, cell adhesion and chemotaxis.…”

Section: Resultsmentioning

confidence: 99%

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Soy Isoflavone Aglycone Modulates A Hematopoietic Response in Combination with Soluble .BETA.-Glucan: SCG

Harada

Masuda

Arii

et al. 2005

Biological & Pharmaceutical Bulletin

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Epidemiological evidence and experimental data from animal studies strongly support the beneficial effects of isoflavones on human health. 1) Isoflavone aglycones (IFAs) are highly bioactive due to their unimpeded intestinal absorption, unlike their related glycosides, which are not absorbed across enterocytes. Glycosylated isoflavones are converted to aglycones via hydorolysis catalyzed by b-glycosidase, an intestinal enzyme that is also commonly found in microorganisms, plants and some basidiomycete mushrooms. In mammalian systems, soy isoflavones exhibit a number of biological activities, including inhibition of cell proliferation, 2,3) antioxidative effects, 4) and enzyme-inhibitory effects. 5) In addition, dietary soy isoflavonoids have been considered for the treatment and prevention of hormone-dependent diseases. 6)An immunomodulating substance, biological response modifier (BRM), or biotherapy, including immunotherapy fields, is important for the treatment of cancer. Some b-glucans are well-known BRMs; the mushrooms from which they are derived are widely distributed in nature and are used as medicine and food.7) Among the b-glucans, 6-branched 1,3-b-glucan is the most well-characterized. We have analyzed the mechanism of b-glucan-mediated immunopharmacological activity and identified the conformation-dependent and -independent activity. 8,9) Sparassis crispa is a medicinal mushroom that recently became cultivatible in Japan. The primary structure of the major the cold NaOH extracted polysaccharide fraction from S. crispa was found to be 6-branched 1,3-b-glucan, having one branch approximately every third main chain. The fraction showed strong antitumor activity against the solid form of Sarcoma 180 in ICR mice.10) In our recently study, we applied S. crispa to several cancer patients in combination with lymphocyte transplantation immunotherapy and obtained a good response.11) To examine the pharmacological applicability of S. crispa b-glucan, a branched b-glucan from Sparassis crispa (SCG) was purified from the cold NaOH extracted fraction, and showed immunopharmacological activities. 11-17)Numerous attempts have been made by scholars to demonstrate the pharmaceutical effect of soy products. However, there have been few studies on their immunomodulatory effect. Dietary soy phytoestrogens may influence the differentiation, signaling and actions of numerous cells of the immune system, as the receptors have been identified on many cell types, including lymphocytes and antigen presenting cells. In fact, there is growing interest in the host immune function, including aspects related to tumor initiation and growth, in addition to other potential health benefits. We have designed this experiment, which is based on the premise that isoflavone may work as a immunomodulating agent. In a previous study, we reported that both oral and intraperitoneal (i.p.) administration of SCG enhanced the hematopoietic response in CY-induced leukopenic mice from a qualitative as well as quantitative point of view. 12,13) In this...

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confidence: 63%

Section: Resultsmentioning

confidence: 99%

Soy Isoflavone Aglycone Modulates A Hematopoietic Response in Combination with Soluble .BETA.-Glucan: SCG

Harada

Masuda

Arii

et al. 2005

Biological & Pharmaceutical Bulletin

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“…The effects of CY are paradoxical in this regard. In a previous study, we demonstrated that both oral and intraperitoneal administration of SCG enhanced the hematopoietic response in CY-induced leukopenia from a qualitative as well as quantitative point of view (11,30). Interleukin-6 production of splenocytes by CY-treated mice was enhanced by the addition of SCG, while cytokines were not induced by SCG in the splenocytes from control mice in vitro.…”

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confidence: 88%

“…and oral (p.o.) routes over a wide range of concentrations (11,30), and the effect was augmented by combination with isoflavone aglycone (10). First, an experiment was performed to confirm the hematopoietic response induced by SCG in CY-induced leukopenia.…”

Section: Effect Of Scg On Leukocyte Number In Cy-treated Micementioning

confidence: 99%

Mechanism of Enhanced Hematopoietic Response by Soluble β‐Glucan SCG in Cyclophosphamide‐Treated Mice

Harada

Kawaminami

Miura

et al. 2006

Microbiology and Immunology

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Immunomodulating substances, biological response modifiers, and biotherapy, including immunotherapy, are important for the treatment of cancer. Some β-glucans are well-known biological response modifiers, and the mushrooms from which they are derived are widely distributed in nature and are used as medicine and food. Among the β-glucans, the 6-branched 1,3-β-glucan is the best characterized. Lentinan from Lentinus edodes (40) and Sonifilan (SPG) from Schizophyllum commune (9) have been used clinically for cancer therapy in Japan. We have analyzed the mechanism of β-glucanmediated immunopharmacological activity, and demonstrated the conformation-dependent and -independent activity of β-glucan (48, 49). Recent data indicated that orally administered β-1,3-glucan potentiated the activity of antitumor monoclonal antibody, leading to enhanced tumor regression and survival (20,21). Thus, cancer immunotherapy using β-glucan is a promising possibility.Sparassis crispa is a medicinal mushroom that recently became cultivatable in Japan. The primary component of the major cold NaOH-extracted polysaccharide fraction from S. crispa was found to be 6-branched 1,3-β-glucan, having one branch approximately every third main chain. This fraction showed strong antitumor activity against the solid form of Sarcoma 180 in ICR mice (34). In our recent study, we used S. crispa to treat several cancer patients in combination with lymphocyte transplantation immunotherapy and obtained a good response (35). To examine the pharmacological usefulness of S. crispa β-glucan Mechanism of Enhanced Hematopoietic

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“…Sparassis crispa was known for its anti-tumor and immunostimulating activities, based on the production of bioactive ß-glucans (47)(48)(49). Only recently has it been shown that a diethyl ether extract of this species inhibits the degradation of IκBα (19).…”

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confidence: 99%

Fungal metabolites modulating NF-κB activity: An approach to cancer therapy and chemoprevention (Review)

Petrova

Reznick²,

Wasser³

et al. 2008

Oncol Rep

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Abstract.Fighting cancer is considered one of the most important areas of research in medicine and immunology. Due to the ability of cancer cells to mutate and become resistant to available drugs, new scientific approaches, focused on molecular mechanisms of carcinogenesis, are needed. A new direction in cancer treatment has arisen, devoted to the adjuvant use of natural bioactive compounds in conventional chemotherapy. This kind of research is gaining more attention. In particular, fungi can be used not only as strong immunoceuticals but also as a source of potent metabolites, capable of penetrating cell membranes and interfering with particular signal transduction pathways linked to processes such as inflammation, cell differentiation and survival, carcinogenesis, and metastasis. One such a crucial pathway involved in the above-mentioned processes, is the activation of the nuclear transcription factor κB (NF-κB). This review compiles the available data on fungal metabolites, known to modulate the activity of NF-κB, thus demonstrating their potential use as novel anti-cancer agents in the rapidly advancing field of molecular therapy. Contents1. Introduction 2. Fungal metabolites modulating NF-κB activity 3. Perspectives IntroductionCancer is the second most predominant cause of death in the modern world, after cardiovascular diseases, taking many human lives every year. Depending on the stage of cancer progression, treatments include surgical operation, radiotherapy and chemotherapy. However, their side effects cause serious damage and suffering to patients. As an alternative to these treatment methods, immunotherapy is now gaining more attention than ever. Immunotherapy substantially reduces the side effects and the inherent pain of cancer sufferred by patients and helps to overcome cancer growth, even in the last stages of the disease.Despite the observed success of most of the chemotherapeutic regimes, cellular adaptations have enabled tumor cells to evade many of these drugs. The nuclear transcription factor κB (NF-κB) is one of the factors responsible for cellular chemoresistance. It is a dimeric transcription factor belonging to the Rel/NF-κB family of transcription factors (1-4). The NF-κB complex is maintained in the cytoplasm in an inactive form by the inhibitory protein κB (IκBα), belonging to a family of inhibitory proteins, IκBs. The major activator of NF-κB is the IκB kinase complex (IKK). This complex is composed of two catalytic subunits, IKK-α and -ß and a regulatory subunit, IKK-γ (also known as NEMO) (2). The NF-κB pathway is triggered by bacterial and viral infections as well as pro-inflammatory cytokines and chemokines [e.g., tumor necrosis factor α (TNF-α), lipopolysaccharide (LPS), interleukins (IL-1, IL-6)], all of which activate the IKK complex. After activation, the IKK complex phosphorylates NF-κB-bound IκBs, thereby targeting them for proteasomal degradation. Simultaneously, the NF-κB dimers are released and free to enter the nucleus where transcriptional activation of target genes be...

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Antitumor Activity and Hematopoietic Response of a b-Glucan Extracted from an Edible and Medicinal Mushroom Sparassis crispa Wulf.: Fr. (Aphyllophoromycetideae)

Cited by 28 publications

References 0 publications

Soy Isoflavone Aglycone Modulates A Hematopoietic Response in Combination with Soluble .BETA.-Glucan: SCG

Soy Isoflavone Aglycone Modulates A Hematopoietic Response in Combination with Soluble .BETA.-Glucan: SCG

Mechanism of Enhanced Hematopoietic Response by Soluble β‐Glucan SCG in Cyclophosphamide‐Treated Mice

Fungal metabolites modulating NF-κB activity: An approach to cancer therapy and chemoprevention (Review)

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