BRD-glucan exhibits potent immunochemotherapeutic activity in vitro and in vivo

Int J Oncol. 2005 Feb;26(2):395-404.

Abstract

We carried out in vitro and in vivo assays to investigate the immunomodulatory and immunochemotherapeutic action mechanism of BRD-glucan, a high molecular weight ( approximately 3,500 kDa) polysaccharide isolated from Aureobasidium sp, and assessed the efficacy of BRD-glucan/adriamycin co-treatment of animal cancer models. RT-PCR and suspension hemolytic, plaque forming, wounding, invasion and cell proliferation assays were utilized to investigate the in vitro immunochemotherapeutic effects of BRD-glucan. In vivo, the effects of BRD-glucan and BRD-glucan/adriamycin co-treatment were tested in a B16 melanoma initiation model and in C57BL/6 mice. In vitro, BRD-glucan did not affect the cellular wounding response or invasion activity; treatment with BRD-glucan led to increase proliferation of B cells, natural killer cells and macrophages, but not T cells. In addition, we found that the BRD-glucan activation of B cells and macrophages was dependent on Toll-like receptor2 (TLR2) and TLR4, which play important roles in innate and adaptive immunity. In vivo, BRD-glucan/adriamycin co-treatment effectively reduced the number and size of metastatic colonies. Based on the results of our in vitro and in vivo toxicity, safety and immunochemotherapy assays, we propose that BRD-glucan is a promising immunochemotherapeutic anti-tumor agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Ascomycota / metabolism
  • B-Lymphocytes / drug effects
  • Cell Line, Tumor
  • Cell Proliferation
  • Chromatography, High Pressure Liquid
  • Combined Modality Therapy / methods*
  • Cytokines / metabolism
  • DNA Primers / chemistry
  • Dose-Response Relationship, Drug
  • Doxorubicin / pharmacology
  • Glucans / therapeutic use*
  • Humans
  • Immunotherapy / methods*
  • Lung / pathology
  • Macrophages / metabolism
  • Magnetic Resonance Spectroscopy
  • Melanoma, Experimental
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Nude
  • Neoplasm Metastasis
  • Polysaccharides / therapeutic use*
  • Receptors, Cell Surface / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes / drug effects
  • Time Factors
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • Wound Healing

Substances

  • Antineoplastic Agents
  • BRD-glucan, Aureobasidium
  • Cytokines
  • DNA Primers
  • Glucans
  • Membrane Glycoproteins
  • Polysaccharides
  • Receptors, Cell Surface
  • TLR2 protein, human
  • TLR4 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • Doxorubicin