Anti-angiogenic and Anti-metastatic Effects of .BETA.-1,3-D-Glucan Purified from Hanabiratake, Sparassis crispa

Abstract

Sparassis crispa (SC), Hanabiratake in Japanese, is an edible mushroom with medicinal properties, which has recently become cultivable in Japan. We have already demonstrated the antitumor and antiallergic activities of this mushroom. 1)SC contains more than 40% of b-D-glucan and it has been reported that its major structural unit are b-(1→3)-D-glucan backbone with single b-(1→6)-D-glucosyl side branching units every three residues.1-3) However, a detailed structure study of b-D-glucan from SC has not been achieved yet by chemical analysis.b-1,3-D-Glucan is a well-documented biological response modifier, 4) and b-D-glucan extracted from SC (SBG) has been reported to possess many biological activities, such as antitumor effects, 1,2) antiallergic effects, 1) improvement of natural killer (NK) cell activity, 1) cytokine-inducing activities in the splenocytes of the mice and human peripheral blood mononuclear cells (PBMC) [5][6][7] and enhancement of hematopoietic responses. 2,[8][9][10] Furthermore, a recent study has suggested the possibility that the application of SBG in cancer patients could be an effective treatment strategy. 11)However, besides immunoenhancing activities, the mechanisms of antitumor activities of b-1,3-D-glucan derived from SC have not been investigated thus far.Angiogenesis is involved not only in the physiological processes such as embryonic development, ovulation and wound healing, but also in many pathological conditions such as solid tumor growth, diabetical retinopathy, age-related maculopathy and rheumatoid arthritis.12-15) Vascular endothelial growth factor (VEGF) is the most prominent angiogenic protein often secreted by the solid tumor cells especially under hypoxic conditions. [16][17][18] Newly formed blood vessels help in tumor progression and promote metastatic spread of the tumor cells. Therefore, anti-angiogenic strategies are considered to be highly effective in cancer therapy. [16][17][18] In the present study, we elucidated the primary structure of SBG using methylation analysis, investigated the anti-angiogenic effects of SBG by using two different animal models, and further assessed the anti-metastatic activities in vivo. We further analyzed the possible mechanisms of SBG function by using human umbilical vein endothelial cells (HUVECs) in vitro. MATERIALS AND METHODS MaterialsDulbecco's modified Eagle's medium (DMEM) was obtained from Nacalai Tesque (Kyoto, Japan). Humedia-EG2 medium was purchased from Kurabo (Osaka, Japan). Antibiotic-antimycotic solutions (100ϫ) containing 10000 units/ml penicillin, 10 mg/ml streptomycin and 25 mg/ml amphotericin B in phosphate-buffered saline (PBS) was purchased from Wako (Osaka, Japan). Fetal bovine serum (FBS) was purchased from Gibco BRL (Auckland, New Zealand). Diffusion chamber ring, MF cement and 13 mm circular membrane filters were obtained from Millipore (Tokyo, Japan). Growth factor reduced phenol red-free Matrigel was obtained from Becton Dickinson & Co. (Franklin Lakes, NJ, U.S.A.). Recombinant mouse VEGF was purchased from...

Anti-Angiogenic Effect of Beta-Glucan Extracted From Pleurotus Spp.

“…β-1,3-D-glucan of SC is reported to act as an antitumor agent in tumor-bearing mice when injected intraperitoneally. [13] Recent studies have revealed that the levels of serum IL-2 and TNF-in Renal cancer-bearing mice were significantly increased by P. eryngii polysaccharide treatment. The increase of IL-2 and TNF-also explain the antitumorigenic properties of P. eryngii polysaccharide.…”

“…[9] Besides to the immunological effects of β-glucan, many studies proved that β-glucan stimulates phagocytic activity as well as synthesis and release of interleukin-1(IL-1), IL-2, IL-4, IL-6, IL-8, IL-13, and tumor necrosis factor-alpha, [10] inhibitory effects on the growth of tumor cells in vivo and affects expression of several important genes in tumor cells, [11] cell cycle arrest and induction of apoptosis can be seen, [12] activated complement receptors on natural killer cells, neutrophils, and lymphocytes may also be associated with the detected tumor cytotoxicity, [8] and finally anti-angiogenic properties. [13] Angiogenesis is a dynamic process of endothelial proliferation and differentiation. Tumors with high angiogenic activity have been correlated with poor patient survival.…”

Vegetative Development of <i>Sparassis crispa</i> in Various Growth Conditions and Effect of Electric Pulse Simulation on Its Fruit Body Production

“…The results obtained from headspace analysis indicate that 3-octanone, DL-3-octanol, and 1-octen-3-ol contribute to the particular aroma of this mushroom [4]. Medicinal properties in S. crispa include anticancer activities‚ antiangiogenic‚ anti-metastatic, wound healing and immune stimulation effects [5]- [7]. It has been recorded that β-glucan content of S. crispa is about 43.6% as measured by enzyme method by Japan Food research laboratories.…”

Морфолого-культуральні властивості рідкісного лікарського гриба Sparassis crispa (Sparassidaceae, Polyporales)

“…Сучасні відомості щодо лікувальних властивостей S. crispa свідчать про широкий біологічний спектр дії цього гриба (Tada et al, 2007;Dalonso et al, 2015). Встановлено, що екстракти, отримані як з плодових тіл, так і міцеліальної маси даного виду, мають імуномодулюючий, онкостатичний і антиметастатичний ефекти (Woodward et al, 1993;Kwon et al, 2009;Yamamoto et al, 2009;Yoshikawa et al, 2010;Takashi, 2013). За умов глибинного і поверхневого культивування штами S. crispa здатні до біосинтезу антибіотиків і цитокінінів (Dyakov et al, 2011;Vedenicheva et al, 2016).…”