The number of mushrooms on Earth is estimated at 140,000, yet maybe only 10% (approximately 14,000 named species) are known. Mushrooms comprise a vast and yet largely untapped source of powerful new pharmaceutical products. In particular, and most importantly for modern medicine, they represent an unlimited source of polysaccharides with antitumor and immunostimulating properties. Many, if not all, Basidiomycetes mushrooms contain biologically active polysaccharides in fruit bodies, cultured mycelium, culture broth. Data on mushroom polysaccharides have been collected from 651 species and 7 infraspecific taxa from 182 genera of higher Hetero- and Homobasidiomycetes. These polysaccharides are of different chemical composition, with most belonging to the group of β-glucans; these have β-(1→3) linkages in the main chain of the glucan and additional β-(1→6) branch points that are needed for their antitumor action. High molecular weight glucans appear to be more effective than those of low molecular weight. Chemical modification is often carried out to improve the antitumor activity of polysaccharides and their clinical qualities (mostly water solubility). The main procedures used for chemical improvement are: Smith degradation (oxydo-reducto-hydrolysis), formolysis, and carboxymethylation. Most of the clinical evidence for antitumor activity comes from the commercial polysaccharides lentinan, PSK (krestin), and schizophyllan, but polysaccharides of some other promising medicinal mushroom species also show good results. Their activity is especially beneficial in clinics when used in conjunction with chemotherapy. Mushroom polysaccharides prevent oncogenesis, show direct antitumor activity against various allogeneic and syngeneic tumors, and prevent tumor metastasis. Polysaccharides from mushrooms do not attack cancer cells directly, but produce their antitumor effects by activating different immune responses in the host. The antitumor action of polysaccharides requires an intact T-cell component; their activity is mediated through a thymus-dependent immune mechanism. Practical application is dependent not only on biological properties, but also on biotechnological availability. The present review analyzes the pecularities of polysaccharides derived from fruiting bodies and cultured mycelium (the two main methods of biotechnological production today) in selected examples of medicinal mushrooms.

https://www.xn--c1atere.xn--p1ai/upload/files/_wasser_polysaccharide.pdf

Medicinal mushrooms as a source of antitumor and immunomodulating polysaccharides.

Chemistry of biologically important synthetic organoselenium compounds.

Over the past two decades, the 5-year survival for ovarian cancer patients has substantially improved owing to more effective surgery and treatment with empirically optimized combinations of cytotoxic drugs, but the overall cure rate remains approximately 30%. Many investigators think that further empirical trials using combinations of conventional agents are likely to produce only modest incremental improvements in outcome. Given the heterogeneity of this disease, increases in long-term survival might be achieved by translating recent insights at the molecular and cellular levels to personalize individual strategies for treatment and to optimize early detection.

/pdf/the-biology-of-ovarian-cancer-new-opportunities-for-11pxy8eu1m.pdf

The biology of ovarian cancer: new opportunities for translation

This review describes pharmacologically active compounds from mushrooms. Compounds and complex substances with antimicrobial, antiviral, antitumor, antiallergic, immunomodulating, anti-inflammatory, antiatherogenic, hypoglycemic, hepatoprotective and central activities are covered, focusing on the review of recent literature. The production of mushrooms or mushroom compounds is discussed briefly.

https://downloads.hindawi.com/journals/ecam/2005/906016.pdf

The pharmacological potential of mushrooms.

Polyamines are essential for the growth and function of normal cells. They interact with various macromolecules, both electrostatically and covalently and, as a consequence, have a variety of cellular effects. The complexity of polyamine metabolism and the multitude of compensatory mechanisms that are invoked to maintain polyamine homoeostasis argue that these amines are critical to cell survival. The regulation of polyamine content within cells occurs at several levels, including transcription and translation. In addition, novel features such as the +1 frameshift required for antizyme production and the rapid turnover of several of the enzymes involved in the pathway make the regulation of polyamine metabolism a fascinating subject. The link between polyamine content and human disease is unequivocal, and significant success has been obtained in the treatment of a number of parasitic infections. Targeting the polyamine pathway as a means of treating cancer has met with limited success, although the development of drugs such as DFMO (alpha-difluoromethylornithine), a rationally designed anticancer agent, has revolutionized our understanding of polyamine function in cell growth and provided 'proof of concept' that influencing polyamine metabolism and content within tumour cells will prevent tumour growth. The more recent development of the polyamine analogues has been pivotal in advancing our understanding of the necessity to deplete all three polyamines to induce apoptosis in tumour cells. The current thinking is that the polyamine inhibitors/analogues may also be useful agents in the chemoprevention of cancer and, in this area, we may yet see a revival of DFMO. The future will be in adopting a functional genomics approach to identifying polyamine-regulated genes linked to either carcinogenesis or apoptosis.

/pdf/a-perspective-of-polyamine-metabolism-5gbwgwozbs.pdf

A perspective of polyamine metabolism.

Polysaccharides extracted from Himematsutake, the fruiting body of Agaricus blazei Murill with hot water were fractionated and purified by ethanol precipitation, ion-exchange chromatography, gel-filtration, affinity chromatography, etc.A total of 17 polysaccharide samples thus obtained were given an antitumor activity test (Sarcoma 180/mice i.p. p.o. method) and traces of their activities through the fractionation and purification processes were found.FI0-a-β, FA-1-a-β, FA-1-a-β, and FA-2-b-β, were obtained as water soluble polysaccharides fractions having great antitumor activities.Analyses of physico-chemical properties and IR- and NMR-spectra of these active fractions showed that their main components were: FI0-a-β, (1 → 6)-; (1 → 3)-β-d-glucan; FA-1-a-α, acidic (1 → 6)-; (1 → 4)-α-d-glucan; FA-1-a-β, acidic (1 → 6)-; (1 → 3)-α-d-glucan; and FA-2-b-β, acidic RNA-protein complex.

https://www.tandfonline.com/doi/pdf/10.1080/00021369.1990.10870406

Antitumor activity and some properties of water-soluble polysaccharides from "Himematsutake", the fruiting body of Agaricus blazei Murill.

Fractionation and antitumor activity of the water-insoluble residue of Agaricus blazei fruiting bodies.

The antitumor activity of the i.p. or p.o. administration of polysaccharide-protein complex, ATOM (antitumor organic substance Mie) prepared from cultured mycelia of Agaricus blazei (Iwade strain 101) "Himematsutake" examined against four kinds of established mouse tumors. ATOM was highly effective at the doses of 10 and 20 mg/kg/day x 10 on subcutaneously implanted Sarcoma 180 in mice, and was also active against Ehrlich ascites carcinoma, Shionogi carcinoma 42 and Meth A fibrosarcoma at doses of 50 and 100 mg/kg/day x 10. ATOM has no direct cytotoxic action on tumor cells in vitro. Thus the tumor growth-inhibitory effect of ATOM is apparently due to immunological host-mediated mechanisms. The number of peritoneal macrophages, the phagocytosis of polystyrene latex beads and the proportion of the third component of complement (C3)-positive fluorescent cells were increased in the mice treated with ATOM. These results suggest that the macrophage activa-tion and alterations of the C3 are necessary for the induction of an antitumor effect of ATOM.

Antitumor effects of a new polysaccharide-protein complex (ATOM) prepared from Agaricus blazei (Iwade strain 101) "Himematsutake" and its mechanisms in tumor-bearing mice.

Inhibitory action of a (1-->6)-beta-D-glucan-protein complex (F III-2-b) isolated from Agaricus blazei Murill ("himematsutake") on Meth A fibrosarcoma-bearing mice and its antitumor mechanism.

SUMMARY: Anti-tumor active polysaccharide against Sarcoma 180 was isolated by DEAESepharose CL-6B and Sepharose 4B column chromatography from the hot-water soluble fraction of the mycelium of liquid-cultured Agaricus blazei mill. This polysaccharide did not react with antibodies of anti-tumor polysaccharides such as lentinan, gliforan, and FIII-2-b which is one of anti-tumor polysaccharides from Agaricus blazei. Moreover, the analyses of 13C-NMR and GC-MS suggested that this polysaccharide was preliminarily glucomannan with a main chain of [g-l,2-1inked D-mannopyranosyl residues and 13-D-glucopyranosyl-3-O13-D-glucopyranosyl residues as a side chain. This polysaccharide was completely different from the anti-tumor polysaccharide from fruiting body ofAgaricus blazei, ~-1,6-glucan.

https://iubmb.onlinelibrary.wiley.com/doi/pdf/10.1080/15216549900201773

Hitoshi Ito

Papers

Antitumor activity and some properties of water-soluble polysaccharides from "Himematsutake", the fruiting body of Agaricus blazei Murill.

Fractionation and antitumor activity of the water-insoluble residue of Agaricus blazei fruiting bodies.

Antitumor effects of a new polysaccharide-protein complex (ATOM) prepared from Agaricus blazei (Iwade strain 101) "Himematsutake" and its mechanisms in tumor-bearing mice.

Inhibitory action of a (1-->6)-beta-D-glucan-protein complex (F III-2-b) isolated from Agaricus blazei Murill ("himematsutake") on Meth A fibrosarcoma-bearing mice and its antitumor mechanism.

Anti-tumor polysaccharide from the mycelium of liquid-cultured Agaricus blazei mill.