The immunomodulating effects of beta-glucan on human immune and cancer cells

Abstract

Many patients with cancer are using complementary medical therapies while having conventional cancer treatments. Herbal extracts are the commonest modality being adopted and Ganoderma lucidum (GL) is the most popular herb used among Orientals. It has been postulated that the GL extracts can stimulate the immune system and exert a cytotoxic effect on cancer cells. The scientific bases of these claims have not been thoroughly investigated previously. In recent years, the active ingredient of the GL fruit body (mycelium) has been identified as beta-glucan. Beta-glucan is a 1 3 linked glucose polymer and is part of the cell-wall components of natural products including fungus (with 1 6 side branches) and bacteria (with 1 4 side branches). Beta-glucan can induce immune response via activating the Dectin-1 receptor, which is mainly found on the surfaces of monocytes, dendritic cells and macrophages. We found that betaglucan from different sources can induce both monocyte proliferation and dendritic cell maturation. With a stringent qualitycontrol process that we adopted, including the determination of actual beta-glucan and endotoxin contents, we found that the potency of beta-glucan seems to directly correlate with the intrinsic size and complexity of the beta-glucan molecule. Purified beta-glucan derived from GL, which is a large and multi-branched molecule, has been consistently noted to be most potent when compared to those derived from other sources. On the other hand, we did not find any direct cytotoxic effects of beta-glucan on a panel of common cancer cell lines tested including carcinoma, sarcoma, and blastoma. It did not trigger any apoptotic pathways and has no effect on the telomerase and telomeric length of the cancer cells. In contrary, it stimulated proliferation of monocytic lineage leukemic cells in-vitro. Hence, its application for patients with leukemia clinically has to be considered with caution. In vivo study of beta-glucan demonstrated its cytotoxic enhancing effect when combined with monoclonal antibody treatment (i.e. neuroblastoma treated with anti-GD2). With its direct stimulating effect on dendritic cells, the potential role of beta-glucan in cancer cellular therapy deserves further exploration.