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

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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.

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Acknowledgments

The study was supported by NIH NCI R25 105012 Collaborative Program in Nutrition and Cancer Prevention; NIH NCCAM and ODS: 1-P50-AT02779 Botanical Research Center for Botanical Immunomodulators, and the Children’s Cancer and Blood Foundation.

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Authors and Affiliations

  1. Cellular Immunology Laboratory, Division of Hematology/Oncology, Department of Pediatrics, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY, 10065, USA

    Hong Lin & Susanna Cunningham-Rundles

  2. Antitumor Assessment Core Facility, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Elisa de Stanchina

  3. Division of Biostatistics and Epidemiology, Department of Public Health, Weill Medical College of Cornell University, New York, NY, USA

    Xi Kathy Zhou

  4. Integrative Medicine Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Feng Hong, Kathleen Wesa & Barrie R. Cassileth

  5. Breast Cancer Medicine Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Andrew Seidman & Monica Fornier

  6. Department of Biological Sciences, Lehman College, City University of New York, New York, NY, USA

    Wei-Lie Xiao & Edward J. Kennelly

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  1. Hong Lin
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Lin, H., de Stanchina, E., Zhou, X.K. et al. Maitake beta-glucan promotes recovery of leukocytes and myeloid cell function in peripheral blood from paclitaxel hematotoxicity. Cancer Immunol Immunother 59, 885–897 (2010). https://doi.org/10.1007/s00262-009-0815-3

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