Maitake beta-glucan enhances therapeutic effect and reduces myelosupression and nephrotoxicity of cisplatin in mice

Int Immunopharmacol. 2009 May;9(5):620-6. doi: 10.1016/j.intimp.2009.02.005. Epub 2009 Feb 26.


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.

MeSH terms

  • Animals
  • Antigens, Fungal / immunology
  • Antigens, Fungal / therapeutic use
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects*
  • Apoptosis / drug effects
  • Bone Marrow / drug effects
  • Bone Marrow / pathology
  • Cell Line, Tumor
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects*
  • Colony-Forming Units Assay
  • Colorectal Neoplasms / blood
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / immunology
  • Colorectal Neoplasms / pathology*
  • Creatinine / blood
  • Drug Synergism
  • Female
  • Grifola*
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Interleukin-12 / genetics
  • Interleukin-12 / immunology
  • Interleukin-12 / metabolism
  • Kidney / drug effects
  • Kidney / pathology
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / pathology
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / immunology
  • Lung Neoplasms / secondary*
  • Lymphocyte Activation / drug effects
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Transplantation
  • Organ Size / drug effects
  • Phytotherapy*
  • beta-Glucans / immunology
  • beta-Glucans / therapeutic use


  • Antigens, Fungal
  • Antineoplastic Agents
  • beta-Glucans
  • Interleukin-12
  • Interferon-gamma
  • Creatinine
  • Cisplatin