Cancer Immunology, Immunotherapy

, Volume 59, Issue 6, pp 885–897

Maitake beta-glucan promotes recovery of leukocytes and myeloid cell function in peripheral blood from paclitaxel hematotoxicity

  • Hong Lin
  • Elisa de Stanchina
  • Xi Kathy Zhou
  • Feng Hong
  • Andrew Seidman
  • Monica Fornier
  • Wei-Lie Xiao
  • Edward J. Kennelly
  • Kathleen Wesa
  • Barrie R. Cassileth
  • Susanna Cunningham-Rundles
Original Article

Abstract

Bone marrow myelotoxicity is a major limitation of chemotherapy. While granulocyte colony stimulating factor (G-CSF) treatment is effective, alternative approaches to support hematopoietic recovery are sought. We previously found that a beta-glucan extract from maitake mushroom Grifola frondosa (MBG) enhanced colony forming unit-granulocyte monocyte (CFU-GM) activity of mouse bone marrow and human hematopoietic progenitor cells (HPC), stimulated G-CSF production and spared HPC from doxorubicin toxicity in vitro. This investigation assessed the effects of MBG on leukocyte recovery and granulocyte/monocyte function in vivo after dose intensive paclitaxel (Ptx) in a normal mouse. After a cumulative dose of Ptx (90–120 mg/kg) given to B6D2F1mice, daily oral MBG (4 or 6 mg/kg), intravenous G-CSF (80 µg/kg) or Ptx alone were compared for effects on the dynamics of leukocyte recovery in blood, CFU-GM activity in bone marrow and spleen, and granulocyte/monocyte production of reactive oxygen species (ROS). Leukocyte counts declined less in Ptx + MBG mice compared to Ptx-alone (p = 0.024) or Ptx + G-CSF treatment (p = 0.031). Lymphocyte levels were higher after Ptx + MBG but not Ptx + G-CSF treatment compared to Ptx alone (p < 0.01). MBG increased CFU-GM activity in bone marrow and spleen (p < 0.001, p = 0.002) 2 days after Ptx. After two additional days (Ptx post-day 4), MBG restored granulocyte/monocyte ROS response to normal levels compared to Ptx-alone and increased ROS response compared to Ptx-alone or Ptx + G-CSF (p < 0.01, both). The studies indicate that oral MBG promoted maturation of HPC to become functionally active myeloid cells and enhanced peripheral blood leukocyte recovery after chemotoxic bone marrow injury.

Keywords

Chemotherapy Hematotoxicity Paclitaxel Beta-glucan Bone marrow and leukocyte recovery Hematopoietic progenitor cells 

Supplementary material

262_2009_815_MOESM1_ESM.doc (71 kb)
Supplementary material (DOC 71KB)

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Hong Lin
    • 1
  • Elisa de Stanchina
    • 2
  • Xi Kathy Zhou
    • 3
  • Feng Hong
    • 4
  • Andrew Seidman
    • 5
  • Monica Fornier
    • 5
  • Wei-Lie Xiao
    • 6
  • Edward J. Kennelly
    • 6
  • Kathleen Wesa
    • 4
  • Barrie R. Cassileth
    • 4
  • Susanna Cunningham-Rundles
    • 1
  1. 1.Cellular Immunology Laboratory, Division of Hematology/Oncology, Department of PediatricsWeill Medical College of Cornell UniversityNew YorkUSA
  2. 2.Antitumor Assessment Core FacilityMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  3. 3.Division of Biostatistics and Epidemiology, Department of Public HealthWeill Medical College of Cornell UniversityNew YorkUSA
  4. 4.Integrative Medicine ServiceMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  5. 5.Breast Cancer Medicine Service, Department of MedicineMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  6. 6.Department of Biological SciencesLehman College, City University of New YorkNew YorkUSA

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