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

Abstract

Non-prescriptional use of medicinal herbs among cancer patients is common around the world. The alleged anti-cancer effects of most herbal extracts are mainly based on studies derived from in vitro or in vivo animal experiments. The current information suggests that these herbal extracts exert their biological effect either through cytotoxic or immunomodulatory mechanisms. One of the active compounds responsible for the immune effects of herbal products is in the form of complex polysaccharides known as beta-glucans. beta-glucans are ubiquitously found in both bacterial or fungal cell walls and have been implicated in the initiation of anti-microbial immune response. Based on in vitro studies, beta-glucans act on several immune receptors including Dectin-1, complement receptor (CR3) and TLR-2/6 and trigger a group of immune cells including macrophages, neutrophils, monocytes, natural killer cells and dendritic cells. As a consequence, both innate and adaptive response can be modulated by beta-glucans and they can also enhance opsonic and non-opsonic phagocytosis. In animal studies, after oral administration, the specific backbone 1-->3 linear beta-glycosidic chain of beta-glucans cannot be digested. Most beta-glucans enter the proximal small intestine and some are captured by the macrophages. They are internalized and fragmented within the cells, then transported by the macrophages to the marrow and endothelial reticular system. The small beta-glucans fragments are eventually released by the macrophages and taken up by other immune cells leading to various immune responses. However, beta-glucans of different sizes and branching patterns may have significantly variable immune potency. Careful selection of appropriate beta-glucans is essential if we wish to investigate the effects of beta-glucans clinically. So far, no good quality clinical trial data is available on assessing the effectiveness of purified beta-glucans among cancer patients. Future effort should direct at performing well-designed clinical trials to verify the actual clinical efficacy of beta-glucans or beta-glucans containing compounds.

Figure 1

β-glucan is one of the key components of the fungal cell wall. The basic subunit of the fungal β-glucan is β-D-glucose linked to one another by 1→3 glycosidic chain with 1→6 glycosidic branches. The length and branches of the β-glucan from various fungi are widely different.

Figure 2

The uptake and subsequent actions of β-glucan on immune cells. β-glucans are captured by the macrophages via the Dectin-1 receptor with or without TLR-2/6. The large β-glucan molecules are then internalized and fragmented into smaller sized β-glucan fragments within the macrophages. They are carried to the marrow and endothelial reticular system and subsequently released. These small β-glucan fragments are eventually taken up by the circulating granulocytes, monocytes or macrophages via the complement receptor (CR)-3. The immune response will then be turned on, one of the actions is the phagocytosis of the monoclonal antibody tagged tumor cells.

Figure 3

Immune activation induced by β-glucans. β-glucans can act on a variety of membrane receptors found on the immune cells. It may act singly or in combine with other ligands. Various signaling pathway are activated and their respective simplified downstream signaling molecules are shown. The reactors cells include monocytes, macrophages, dendritic cells, natural killer cells and neutrophils. Their corresponding surface receptors are listed. The immunomodulatory functions induced by β-glucans involve both innate and adaptive immune response. β-glucans also enhance opsonic and non-opsonic phagocytosis and trigger a cascade of cytokines release, such as tumor necrosis factor(TNF)-α and various types of interleukins (ILs).