Maitake beta-glucan enhances therapeutic effect and reduces myelosupression and nephrotoxicity of cisplatin in mice.
Cisplatin is broadly used clinically as an anticancer drug. Despite its significant anticancer activity, cisplatin-induced nephrotoxicity and myelosuppression limit its use. MD-Fraction is glucan purified from maitake (Grifola frondosa), which has beta-1, 6-main chain with beta-1, 3-branches, has been reported to exhibit antitumor and antimetastatic activities by enhancing the immune system. In this study, we demonstrate that MD-Fraction in combination with cisplatin significantly enhanced antitumor and antimetastatic activity compared to cisplatin alone. MD-Fraction reduced decreases in body weight, spleen weight and the number of immunocompetent cells such as macrophages, DCs and NK cells in cisplatin-treated mice. MD-Fraction also induced IL-12p70 production by splenocytes, resulting in increased NK cell activity in cisplatin-treated mice. MD-Fraction significantly increased the mRNA expression of GM-CSF, G-CSF, M-CSF, IFN-gamma, IL-12 p40 in splenocytes and reduced the decrease in the number of CFU-GM colonies in cisplatin-treated bone marrow. These facts suggest that MD-Fraction can reduce cisplatin-induced myelosuppression. Moreover, treatment with MD-Fraction significantly reduced cisplatin-induced nephrotoxicity accompanied by increases in serum creatinine level, necrosis and apoptosis of renal tubular cells. These results suggest that MD-Fraction in combination with cisplatin cannot only enhance antitumor and antimentastatic acitivity, but also reduce cisplatin-induced myelotoxicity and nephrotoxicity.
Masuda
Yuki
Y
Department of Microbial Chemistry, Kobe Pharmaceutical University, Kobe, Japan. micro-s@kobepharma-u.ac.jp
Inoue
Munechika
M
Miyata
Ayu
A
Mizuno
Shigeto
S
Nanba
Hiroaki
H
D000818:Animals; D000946:Antigens, Fungal / Q000276:immunology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D017209:Apoptosis / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects*; D003114:Colony-Forming Units Assay; D015179:Colorectal Neoplasms / Q000097:blood / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D003404:Creatinine / Q000097:blood; D004357:Drug Synergism; D005260:Female; D048691:Grifola; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000556:secondary*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009929:Organ Size / Q000187:drug effects; D008517:Phytotherapy; D047071:beta-Glucans / Q000276:immunology / Q000627:therapeutic use
D000946:Antigens, Fungal; D000970:Antineoplastic Agents; D047071:beta-Glucans; D018664:Interleukin-12; D007371:Interferon-gamma; D003404:Creatinine; D002945:Cisplatin