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

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 B6D2F1 mice, 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.

Cecropin Suppresses Human Hepatocellular Carcinoma BEL-7402 Cell Growth and Survival in vivo without Side-Toxicity

“…Traditional chemotherapeutics often causes hematotoxicity when administrated against cancer (Lin et al, 2010;Huang et al, 2013). In the present study, we found that cecropin treatment had no influence on hematological phenotype including Hb content, WBC and RBC count, as well as PCV in BEL-7402 tumor-beared mice as compared with saline treatment.…”

Polysaccharide Production by Submerged Fermentation

“…Those β-glucans with β-(1!3, 1!4) obtained from the yeast Saccharomyces cerevisiae present antiparasitic, antibacterial, antiviral, antifungal, antimutagenic, and antitumor activities, among others (Zong et al 2012). Those ones isolated from different fungi such as Auricularia polytricha, Grifola frondosa, Candida albicans, Poria cocos, Agaricus blazei, Lentinus edodes, Schizophyllum commune, and Coriolus versicolor exhibit antitumor, immunomodulatory, and antimutagenic properties (Mantovani et al 2008;Lin et al 2010;Carneiro et al 2013;Zhang et al 2013).…”

“…According to several reports (Pan et al 2012(Pan et al , 2013, the polysaccharidic extracts from G. lucidum present antioxidant activity and improve the immunity, so they have been suggested for the treatment of gastric cancer. The β-glucan from the macromycetes Grifola frondosa (known as Maitake beta-glucan or MBG) has been applied as coadjuvant for cancer treatment like chemotherapy (Lin et al 2010).…”

Immunomodulatory effects of mushroom β-glucans

“…Peripheral blood mononuclear cells (PBMCs), bone marrow-derived macrophages and DCs, alveolar macrophages, spleen cells and epithelial cell lines like the Caco-2 have all also been used (Chaung et al, 2009;Lin et al, 2010;Volman et al, 2010). Different forms of mushroom β-glucans, for instance, crude mushroom extract (Guo et al, 2004), pure isolated native β-glucans (Lin et al, 2005;Kupfahl et al, 2006;Lin et al, 2010), modified isolated β-glucans (Rice et al, 2005) and fractionated β-glucans (Inoue et al, 2002), have been examined for their immunomodulating properties.…”