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International Journal of Medicinal Mushrooms
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ISSN Imprimer: 1521-9437
ISSN En ligne: 1940-4344

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International Journal of Medicinal Mushrooms

DOI: 10.1615/IntJMedMushr.v9.i2.20
pages 109-122

Immunomodulation and Antitumor Activity of a Mushroom Product, Proflamin, Isolated from Flammulina velutipes (W. Curt.: Fr.) Singer (Agaricomycetideae)

Hirofumi Maruyama
Japanese Association for Integrative Medicine, Kandakonya-cho, Tokyo, Japan
Tetsuro Ikekawa
Japanese Association of Integrative Medicine (JAIM). Association for Popularization of Integrative Medicine and Treatments (NPO, Japan), Sanshin Building, 3F, 2-15-14 Uchikanda, Chiyoda-ku, Tokyo 101-0047,Japan


Proflamin (PRF), an antitumor agent, is orally effective against the syngeneic tumor in mice and is a biological response modifier obtained from an edible mushroom. It has been isolated from the mycelia of Flammulina velutipes (W. Curt.: Fr.) Singer and is an acidic glycoprotein containing more than 90% protein and less than 10% carbohydrate; its molecular weight is 13,000 ± 4000. PRF greatly increases the lifespan of mice implanted with the syngeneic tumors, B-16 melanoma and adenocarcinoma 755 and inhibits the growth of solid tumors of Sarcoma 180 (S-180) by so-called "host-mediated" antitumor activities. PRF inhibited the growth of S-180 or L1210 leukemia ascite cells in combination with the S-180 solubilized vaccine or glutaraldehyde and Con A-bound L1210 vaccine and showed strong antitumor activity when a combination therapy was given with surgical treatment in mice bearing Meth-A fibrosarcoma (Meth-A). The combination therapy with cryosurgery and PRF was found to abolish the suppression of tumor immunocompetence at 2 weeks after cryosurgery, and it exhibited no toxic actions either in vitro or in vivo. Oral administration of PRF significantly intensified various immunoresponses in tumor-bearing mice, but it was not very effective against the immunity of healthy (non-tumor-bearing) mice. The effective dose range for immunomodulation was rather wide (1−30 mg/kg), and the optimum dose was supposed to be about 10 mg/kg when administered PO, consecutively. These doses were almost the same as those for the treatment of tumors in the mice mentioned above. A protein-bound polysaccharide, EA6, was also isolated from fruit bodies of F. velutipes. Treatment with EA6 after the surgery remarkably inhibited growth of the rechallenged Meth-A solid tumor, and the effect was mediated by CD4+ T cells. Furthermore, EA6 augmented the humoral immunity, cellular immunity, and IL-2 production against Meth-A tumor antigen after surgery.