Maitake D-Fraction enhances antitumor effects and reduces immunosuppression by mitomycin-C in tumor-bearing mice.
OBJECTIVE
D-Fraction, a polysaccharide extracted from maitake mushrooms (Grifola frondosa), has been reported to exhibit an antitumor effect through activation of immunocompetent cells, including macrophages and T cells, with modulation of the balance between T-helper 1 and 2 cells. We examined whether D-Fraction could decrease the effective dosage of the chemotherapeutic agent, mitomycin-C (MMC), necessary to control carcinoma in mice.


RESULTS
We determined that 0.25 mg.kg-1.d-1 was the optimal dosage of MMC because consecutive administration for 17 d resulted in antitumor effects and a survival ratio of 100% in mice bearing mammary cancer cells (MM-46). Although the dosage of MMC was lower than the effective level, spleen weight and total number of nuclear cells in the mouse spleen decreased, indicating that MMC showed immunosuppressive activity. In contrast, the combination of D-Fraction and MMC recovered the decreases in the dose response induced by MMC and inhibited tumor cell growth more than MMC alone. These effects were achieved through increased immunocompetent cell proliferation. We evaluated the expression of CD28 on splenic CD8+ T cells and the amount of interleukin-12 produced by whole spleen cells including macrophages after administering D-Fraction. The results showed enhancement of the T-helper 1 dominant response.


CONCLUSIONS
These results suggest that D-Fraction can decrease the effective dosage in tumor-bearing mice by increasing the proliferation, differentiation, and activation of immunocompetent cells and thus provide a potential clinical benefit for patients with cancer.
Kodama
Noriko
N
Department of Microbial Chemistry, Kobe Pharmaceutical University, Kobe, Japan. n-kodama@kobepharma-u.ac.jp
Murata
Yukihito
Y
Asakawa
Akihiro
A
Inui
Akio
A
Hayashi
Masahiko
M
Sakai
Norio
N
Nanba
Hiroaki
H
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D002277:Carcinoma / Q000188:drug therapy* / Q000276:immunology / Q000628:therapy; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D048691:Grifola / Q000737:chemistry*; D007111:Immunity, Cellular / Q000187:drug effects; D007167:Immunotherapy / Q000379:methods; D008264:Macrophages / Q000378:metabolism; D008297:Male; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy* / Q000276:immunology / Q000628:therapy; D051379:Mice; D008809:Mice, Inbred C3H; D016685:Mitomycin / Q000627:therapeutic use*; D011134:Polysaccharides / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D014408:Biomarkers, Tumor; D011134:Polysaccharides; D016685:Mitomycin