BRD-glucan exhibits potent immunochemotherapeutic activity in vitro and in vivo.
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.
Moon
Seong-Hoon
SH
Korea Research Institute of Bioscience and Biotechnology, Yuseong, Daejeon 305-333, Korea.
Heo
Jin-Chul
JC
Fine
Robert L
RL
Kim
Hwan-Mook
HM
Kim
Sung-Uk
SU
Yoon
Byung-Dae
BD
Lee
Sang-Han
SH
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001203:Ascomycota / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002851:Chromatography, High Pressure Liquid; D003131:Combined Modality Therapy / Q000379:methods*; D016207:Cytokines / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology; D005936:Glucans / Q000627:therapeutic use*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008168:Lung / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008546:Melanoma, Experimental; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D011134:Polysaccharides / Q000627:therapeutic use*; D011956:Receptors, Cell Surface / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000187:drug effects; D013997:Time Factors; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014945:Wound Healing
D000970:Antineoplastic Agents; C502277:BRD-glucan, Aureobasidium; D016207:Cytokines; D017931:DNA Primers; D005936:Glucans; D008562:Membrane Glycoproteins; D011134:Polysaccharides; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D004317:Doxorubicin