Anti-cancer ‘shroom?

Agaricus subrufescens (misidentified as Agaricus blazei, Agaricus sylvaticus) is a species of mushroom, commonly known as Agaricus Blazei Murill Mushroom, Almond mushroom, or himematsutake (Japanese: ???, “princess matsutake”) and by a number of other names. Agaricus subrufescens is a choice edible, with a somewhat sweet taste and fragrance of almonds. This mushroom is also well known as a medicinal mushroom, for its purported medicinal properties, due to research which indicates it may stimulate the immune system.

Taxonomy
Agaricus subrufescens was first described by the American botanist Charles Horton Peck in 1893.[1] During the late 19th and early 20th century, it was cultivated for the table in the eastern United States.[2] It was discovered again in Brazil during the 1970s, and misidentified as Agaricus blazei Murrill, a species originally described from Florida. It was soon marketed for its purported medicinal properties under various names, including ABM (for Agaricus blazei Murill), Cogumelo do Sol (mushroom of the sun), Cogumelo de Deus (mushroom of God), Cogumelo de Vida (mushroom of life), Himematsutake, Royal Sun Agaricus, Mandelpilz, and Almond Mushroom.

In 2002, Didukh and Wasser correctly rejected the name A. blazei for this species, but unfortunately called the Brazilian fungus A. brasiliensis,[3] a name that had already been used for a different species, Agaricus brasiliensis Fr. (1830). Richard Kerrigan undertook genetic and interfertility testing on several fungal strains[2] and showed that samples of the Brazilian strains called A. blazei and A. brasiliensis were genetically similar to, and interfertile with, North American populations of Agaricus subrufescens. These tests also found European samples called A. rufotegulis to be of the same species. Because A. subrufescens is the oldest name, it has taxonomical priority.

Note that Agaricus blazei Murrill is a perfectly valid name, but for a completely different mushroom. Agaricus silvaticus Schaeff. is also a perfectly valid name for a common, north temperate, woodland mushroom. Neither is a synonym of Agaricus subrufescens.

Description

The floccose stipe and annulus of A. subrufescensThe cap is initially hemispherical, later becoming convex, with a diameter of 5 to 18 centimetres (2.0 to 7.1 in).[4] The cap surface is covered with silk-like fibers, although in maturity it develops small scales (squamulose). The color of the cap may range from white to grayish or dull reddish-brown; the cap margin typically splits with age. The flesh of A. subrufescens is white, and has the taste of “green nuts”, with the odor of almonds.[4] The gills are not attached to the stalk (free), narrow, and crowded closely together. They start out whitish in color, then later pinkish and finally black-brown as the spores mature. Spores are ellipsoid, smooth, dark-purplish brown when viewed microscopically, with dimensions of 6–7.5 by 4–5 µm. The stipe is 6 to 15 centimetres (2.4 to 5.9 in) by 1 to 1.5 centimetres (0.39 to 0.59 in) thick, and bulbous at the base. Initially solid, the stipe becomes hollow with age; it is cottony (floccose) to scaly towards the base.[4] The annulus is abundant and double-layered; it is bent downwards towards the stem, smooth and whitish on the upper side, and covered with cottony scales on the lower side.

Distribution and habitat
Agaricus subrufescens forms fruitbodies singly or in clusters in leaf litter in rich soil, often in domestic habitats.[5] It was originally described from the northeastern United States, but has been found growing in California, Hawaii, Great Britain, the Netherlands, Israel, Taiwan, and Brazil.[2]

Edibility
Aroma
Agaricus subrufescens is a choice edible, with a somewhat sweet taste and fragrance of almonds. The almond smell of the mushroom is mostly due to the presence of benzaldehyde, benzyl alcohol, benzonitrile, and methyl benzoate.[6]

Commercial use
Due to the fact Agaricus subrufescens contains a high level of beta glucans, compounds known for stimulating the immune system,[7][8][9] the fungus is used in oncological therapy in Japan and Brazil.[10] In addition to beta-glucans, the mushroom’s effect on the immune system is believed to be due to other polysaccharides such as alpha-glucans.[11] In Japan, Agaricus subrufescens is sold under the brand names Sen-Sei-Ro Gold, and ABMK, and is used by an estimated 500,000 people[12] In Japan, Agaricus subrufescens is also the most popular complementary and alternative medicine used by cancer patients.[13] Although Agaricus subrufescens is cultivated in the United States, the largest exporters are China and Brazil. It has been noted in a scientific review of A. subrufescens research,[14] that the range of quality in A. subrufescens cultivation can affect the mushroom’s ability to impact cells of the immune system.

Recently, Watanabe et al. published a report in the Biological & Pharmaceutical Bulletin on a novel hybrid of A. subrufescens called Basidiomycetes-X (BDM-X)[15] and a US patent[16] was issued on a novel hybrid of the A. subrufescens edible mushroom which was cross-bred (hybridized) with another medicinal mushroom resulting in a new hybrid claimed to possess 10 to 3000 times the potency of similar but unpatented mushrooms.

Research
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Many researchers have studied Agaricus subrufescens, as well as other medicinal mushrooms for close to 50 years, due to laboratory tests which show they may stimulate immune system cells and the production of immune system cytokines. Below is a summary of this research, which is often based on animal or cellular models. Research conducted on the mushroom’s ability to impact the human immune system or human diseases is limited.[17]

Cancer research
Animal and cellular research has shown that Agaricus subrufesscens application or consumption appears to offer anti-cancer properties.

Experimental Model Experimental Effect (Cell culture) Experimental Effect (Animal research) Experimental Effect (Clinical)
Colorectal cancer Benefited hematological and immunological parameters[18]
Fibrosarcoma Inhibited growth via apoptosis[19] Inhibited growth[19]
Sarcoma Inhibited angiogenesis. Inhibited growth[20][12][21]
Gynaecological cancer Increased NK cell activity, quality of life[22]
Ovarian cancer Inhibited growth and metastasis via apoptosis induction[23] Inhibited metastasis, growth[23]
Lung cancer Inhibited growth via apoptosis[24] Inhibited metastasis, growth[23]
Leukaemia Inhibited growth via apoptosis[25][26][27] Inhibited growth[25][28]
Myeloma Inhibited growth[29]
Hepatocarcinoma Inhibited abnormal collagen formation[30][31] Inhibited growth[32]
Stomach cancer Inhibited growth via apoptosis[24][33]
Prostate cancer Inhibited growth via apoptosis[34] Inhibited growth[34]
Skin cancer Inhibited growth[1] when applied orally or topically

Immune system
Cellular and animal research has shown that Agaricus subrufescens may stimulate immune system cells and the production cytokines, like interferons and interleukins (reviewed by G. Hetland).[35]

Direct anti-viral properties
Agaricus subrufescens mushrooms are known to have anti-viral properties in cell culture.[36][37] The ability of Agaricus subrufescens to inhibit viruses in the human body has not been studied. Other mushrooms are also known to have anti-viral, anti-bacterial, and anti-fungal activity in cell culture.[38][38][39][40][41][42][43][44]

Other possible effects
Besides evidence Agaricus subrufescens may up-regulate the immune system, additional research suggests the mushroom has a beneficial effect on cholesterol,[45] inhibiting pathogenic factors,[46][47][48][49] and inhibiting angiogenesis.[21][50]

Limited clinical and animal research suggests, Agaricus subrufescens consumption may lower blood glucose levels and improve insulin resistance.[45][51][52][18]

References
^ Peck CH. (1893). “Report of the Botanist (1892)”. Annual Report on the New York State Museum of Natural History 46: 85–149.
^ a b c Kerrigan, RW (2005). “Agaricus subrufescens, a cultivated edible and medicinal mushroom, and its synonyms.”. Mycologia 97 (1): 12–24. doi:10.3852/mycologia.97.1.12. PMID 16389952.
^ Wasser, Solomon P.; Didukh, Marina Ya.; de Amazonas, Maria Angela L.; Nevo, Eviatar; Stamets, Paul; da Eira, Augusto F. (2002). “Is a Widely Cultivated Culinary-Medicinal Royal Sun Agaricus (the Himematsutake Mushroom) Indeed Agaricus blazei Murrill?”. International Journal of Medicinal Mushrooms 4 (4): 267–290. OCLC 39977461. http://www.theliterature.org/The_Fifth_Kingdom/International%20Journal%20of%20Medicinal%20Mushrooms/10609965.pdf.
^ a b c Murrill, W. A. (1922). “Dark-Spored Agarics: III. Agaricus”. Mycologia 14 (4): 200. doi:10.2307/3753642.
^ Smith, Alexander Hanchett (1975). A Field Guide to Western Mushrooms. Ann Arbor, Mich: University of Michigan Press. p. 228. ISBN 0-472-85599-9. [page needed]
^ Chen, CHU-CHIN; Wu (1984). “Volatile Components of Mushroom (Agaricus subrufecens)”. Journal of Food Science 49: 1208. doi:10.1111/j.1365-2621.1984.tb10433.x.
^ Hetland, Geir; Sandven, P. (2002). “beta-1,3-Glucan reduces growth of Mycobacterium tuberculosis in macrophage cultures”. FEMS Immunology and Medical Microbiology 33 (1): 41. doi:10.1111/j.1574-695X.2002.tb00570.x. OCLC 27447797. PMID 11985967.
^ Morikawa, Kaoru; Takeda, Reiko; Yamazaki, Masatoshi; Mizuno, Den’Ichi (1985). “Induction of Tumoricidal Activity of Polymorphonuclear Leukocytes by a Linear {beta}-1,3-D-Glucan and Other Immunomodulators in Murine Cells”. Cancer Research 45 (4): 1496. PMID 3156669. http://cancerres.aacrjournals.org/cgi/reprint/45/4/1496.
^ Amino, M; Noguchi; Yata; Matsumura; Hirayama; Abe; Enomoto; Asato (1983). “Studies on the effect of lentinan on human immune system. II. In vivo effect on NK activity, MLR induced killer activity and PHA induced blastic response of lymphocytes in cancer patients”. Gan to kagaku ryoho. Cancer & chemotherapy 10 (9): 2000–6. PMID 6225393.
^ Weil, Andrew (2002). “Mushrooms to Curb Cancer?”. http://www.drweil.com/drw/u/id/QAA68312. [self-published source?]
^ Firenzuoli, F; Gori; Lombardo (2008). “The Medicinal Mushroom Agaricus blazei Murrill: Review of Literature and Pharmaco-Toxicological Problems.”. Evidence-based complementary and alternative medicine : eCAM 5 (1): 3–15. doi:10.1093/ecam/nem007. PMID 18317543.
^ a b Takaku, T; Kimura; Okuda (2001). “Isolation of an antitumor compound from Agaricus blazei Murill and its mechanism of action.”. The Journal of nutrition 131 (5): 1409–13. PMID 11340091.
^ Hyodo I, Amano N, Eguchi K, Narabayashi M, Imanishi J, Hirai M et al. (2005). “Nationwide survey on complementary and alternative medicine in cancer patients in Japan.”. J Clin Oncol 23 (12): 2645–54. doi:10.1200/JCO.2005.04.126. PMID 15728227. http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15728227.
^ Hetland, G; Johnson; Lyberg; Bernardshaw; Tryggestad; Grinde (2008). “Effects of the medicinal mushroom Agaricus blazei Murill on immunity, infection and cancer.”. Scandinavian journal of immunology 68 (4): 363–70. doi:10.1111/j.1365-3083.2008.02156.x. PMID 18782264.
^ Watanabe, T; Nakajima; Konishi (2008). “In vitro and in vivo anti-oxidant activity of hot water extract of basidiomycetes-X, newly identified edible fungus.”. Biological & pharmaceutical bulletin 31 (1): 111–7. doi:10.1248/bpb.31.111. PMID 18175952.
^ US patent 6120772, Ito, Hitoshi; Sumiya, Toshimitsu, “Oral drugs for treating AIDS patients”, granted 19 September 2000
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^ a b Fujimiya Y, Suzuki Y, Oshiman K, Kobori H, Moriguchi K, Nakashima H, Matumoto Y, Takahara S, Ebina T, Katakura R (May 1998), “Selective tumoricidal effect of soluble proteoglucan extracted from the basidiomycete, Agaricusblazei Murill, mediated via natural killer cell activation and apoptosis.”, Cancer Immunol Immunother (Springer Verlag) 46 (3): 147–159, doi:10.1007/s002620050473, ISSN 0340-7004, PMID 9625538
^ Gonzaga ML, Bezerra DP, Alves AP, et al. (January 2009), “In vivo growth-inhibition of Sarcoma 180 by an alpha-(1–>4)-glucan-beta-(1–>6)-glucan-protein complex polysaccharide obtained from Agaricus blazei Murill”, Nat Med (Tokyo) 63 (1): 32–40, doi:10.1007/s11418-008-0286-4, ISSN 1340-3443, PMID 18726068
^ a b Niu YC, Liu JC, Zhao XM, Wu XX (January 2009), “A low molecular weight polysaccharide isolated from Agaricus blazei suppresses tumor growth and angiogenesis in vivo”, Oncol. Rep. 21 (1): 145–52, ISSN 1021-335X, PMID 19082455
^ Ahn WS, Kim DJ, Chae GT, Lee JM, Bae SM, Sin JI, Kim YW, Namkoong SE, Lee IP (July-August 2004), “Natural killer cell activity and quality of life were improved by consumption of a mushroom extract, Agaricus blazei Murill Kyowa, in gynecological cancer patients undergoing chemotherapy”, Int J Gynecol Cancer 14 (4): 589–94, doi:10.1111/j.1048-891X.2004.14403.x, ISSN 1048-891X, PMID 15304151
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^ a b Itoh H, Ito H, Hibasami H (December 2008), “Blazein of a new steroid isolated from Agaricus blazei Murrill (himematsutake) induces cell death and morphological change indicative of apoptotic chromatin condensation in human lung cancer LU99 and stomach cancer KATO III cells”, Oncol. Rep. 20 (6): 1359–61, ISSN 1021-335X, PMID 19020714
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^ Jin CY, Moon DO, Choi YH, Lee JD, Kim GY (August 2007), “Bcl-2 and caspase-3 are major regulators in Agaricus blazei-induced human leukemic U937 cell apoptosis through dephoshorylation of Akt.”, Biol Pharm Bull 30 (8): 1432–1437, doi:10.1248/bpb.30.1432, ISSN 0918-6158, PMID 17666799, http://www.jstage.jst.go.jp/article/bpb/30/8/1432/_pdf
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^ Tian, X (1994), “Clinical observation on treatment of acute nonlymphocytic leukemia with Agaricus blazei Murill”, Journal of Lanzhou University (Medical Sciences) 20: 169–171, ISSN 1000-2812, PMID not listed in PubMed) (journal not listed in PubMed)
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^ Sorimachi, K; Ikehara; Maezato; Okubo; Yamazaki; Akimoto; Niwa (2001). “Inhibition by Agaricus blazei Murill fractions of cytopathic effect induced by western equine encephalitis (WEE) virus on VERO cells in vitro.”. Bioscience, biotechnology, and biochemistry 65 (7): 1645–7. doi:10.1271/bbb.65.1645. PMID 11515550.
^ Chen, L; Shao; Su (2004). “Coimmunization of Agaricus blazei Murill extract with hepatitis B virus core protein through DNA vaccine enhances cellular and humoral immune responses.”. International immunopharmacology 4 (3): 403–9. doi:10.1016/j.intimp.2003.12.015. PMID 15037217.
^ Chen, L; Shao (2006). “Extract from Agaricus blazei Murill can enhance immune responses elicited by DNA vaccine against foot-and-mouth disease.”. Veterinary immunology and immunopathology 109 (1-2): 177–82. doi:10.1016/j.vetimm.2005.08.028. PMID 16213597.
^ Tryggestad AMA, Espevik T, Forland DT, Ryan L, Hetland G (2007). “The medical mushroom Agaricus blazei Murill activates NF-?B via TLR2″. 13th International Congress of Immunology (Rio de Janeiro: Medimond): 2–23.
^ Kimura, Y; Kido; Takaku; Sumiyoshi; Baba (2004). “Isolation of an anti-angiogenic substance from Agaricus blazei Murill: its antitumor and antimetastatic actions.”. Cancer science 95 (9): 758–64. doi:10.1111/j.1349-7006.2004.tb03258.x. PMID 15471563.
^ Kim, YW; Kim; Choi; Lee (2005). “Anti-diabetic activity of beta-glucans and their enzymatically hydrolyzed oligosaccharides from Agaricus blazei.”. Biotechnology letters 27 (7): 483–7. doi:10.1007/s10529-005-2225-8. PMID 15928854.
^ Hsu, CH; Liao; Lin; Hwang; Chou (2007). “The mushroom Agaricus Blazei Murill in combination with metformin and gliclazide improves insulin resistance in type 2 diabetes: a randomized, double-blinded, and placebo-controlled clinical trial.”. Journal of alternative and complementary medicine (New York, N.Y.) 13 (1): 97–102. doi:10.1089/acm.2006.6054. PMID 17309383.
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