Research Progress on the Antitumor Effects of Beta Glucan

Beta glucan is a biological macromolecule widely distributed in fungi, bacteria, and plants. It is an essential structural component of the cell walls of various organisms. β-glucan possesses multiple biological activities, including antitumor, leukocyte-promoting, complement-activating, antiviral, anticoagulant, and immunostimulatory properties. It can activate macrophages, promote cytokine synthesis, and induce nitric oxide (NO) production, thereby exhibiting a broad spectrum of biological activities. During interactions among different organisms, β-glucan also demonstrates diverse biological effects, such as stimulating the immune system in animals. This article provides a comprehensive overview of the sites, pathways, and mechanisms underlying the antitumor effects of β-glucan.

1. Antitumor Effect of β-Glucan

1.1 Site of Action

1.1.1 In Vitro Antitumor Effect of β-Glucan

β-Glucan exhibits direct cytotoxic activity against tumor cells in vitro — it can directly kill cancer cells outside the body without harming normal animal cells. This characteristic makes it superior to other cytotoxic antitumor drugs.

Under a microscope, S180 ascites tumor cells treated with Pleurotus ostreatus polysaccharides gradually swell, and small vesicle-like protrusions appear on the cell membrane. Within one hour, the cells completely rupture, whereas spleen, liver, kidney, and thymus cells remain intact and unharmed. In vitro experiments showed that Ganoderma lucidum polysaccharides inhibited the proliferation of various tumor cells, including Ehrlich ascites carcinoma (AH-B), ascitic hepatoma, sarcoma S, leukemia L, and leukemia P368, to varying degrees.

1.1.2 In Vivo Antitumor Effect of β-Glucan

Numerous pharmacological experiments have demonstrated that most β-glucans possess antitumor activity in vivo. Although there are many reports on the composition and structure of Lentinus edodes (shiitake) polysaccharides, it has been confirmed that only β-glucan shows a structural relationship with immunoactivity. Shiitake polysaccharides exhibit significant inhibitory effects on solid tumors. When S180 and H22 ascitic tumor-bearing mice were administered 4.35 mg/kg of shiitake polysaccharide intraperitoneally each day, the inhibition rates were 47% and 40%, respectively, and the survival periods of the tumor-bearing mice were extended by 8 days and 10 days.

According to Chinara G, shiitake polysaccharides exhibit inhibitory activity against the growth of various homologous and spontaneous tumors, as well as heterologous tumors (such as sarcoma 180). In addition, they can also prevent tumor metastasis induced by chemical and viral carcinogens.

Table 1: Sources, Types, and Main Pharmacological Effects of Selected Fungal Polysaccharides

1.2 Mechanism of Action

Polysaccharides with cytotoxic properties can directly kill tumor cells. Experimental studies have shown that β-glucan from Grifola frondosa (Maitake mushroom) exhibits a stronger direct tumoricidal effect than the widely used spore powder of Ganoderma lucidum (Reishi mushroom).

As biological immunomodulators, β-glucans can indirectly inhibit or kill tumor cells by enhancing the immune function of the host. β-glucans promote the activity of lymphokine-activated killer (LAK) cells and natural killer (NK) cells, and induce macrophages to produce tumor necrosis factors (TNF), thereby exerting host-mediated antitumor effects. Studies by Taek et al. have shown that β-glucans can suppress tumor metastasis by activating macrophages and enhancing the cytotoxic activity of NK cells.

2. Mechanism of the Antitumor Activity of β-Glucan

Since Brander reported in 1958 that yeast cell wall polysaccharide (Zymosan) possesses antitumor properties, numerous immunological studies have demonstrated that β-glucans can activate immune cells such as T cells, B lymphocytes, macrophages (M), and natural killer (NK) cells. β-glucans can also enhance complement activity, promote the production of cytokines, and regulate multiple aspects of immune system function.

The polysaccharides of Ganoderma lucidum (Reishi mushroom) are mainly composed of glucans and glycoproteins. The mechanisms underlying their antitumor activity are not yet fully established. Currently, three representative hypotheses exist: the immunomodulation theory, the ribosome-inactivating protein theory, and the differentiation theory.

The immunomodulation theory proposes that β-glucans exert antitumor effects by enhancing the host’s immune functions, a view that has been confirmed by many researchers.

The ribosome-inactivating protein theory was proposed in recent years by the Shanghai Institute of Materia Medica after extensive experimental studies. This theory suggests that compounds extracted from Ganoderma lucidum can cause the ribosomes of tumor cells to lose activity, thereby inhibiting or preventing their normal cell division.

The differentiation theory was proposed by Professor Zhang Yaotong from Dalian Medical University. His research indicates that under the influence of differentiation-promoting agents, tumor cells can re-differentiate into normal cells, reversing their malignant state. This discovery opens up a new, non-cytotoxic approach and a novel pathway for cancer treatment.

3. Clinical Applications of Fungal Polysaccharides

In recent years, β-glucan has attracted increasing attention as an important target for industrial development. A variety of promising antitumor agents have been developed from natural products, including taxol, camptothecin, vincristine, polysaccharides, active peptides, and terpenoids. Among these, natural polysaccharides have shown significant therapeutic effects and have aroused great interest due to their low toxicity and lack of side effects. For example, shiitake polysaccharides have already entered the stage of clinical application, and polysaccharide-based antitumor drugs have been commercialized in both China and Japan.

In Japan, Ganoderma lucidum extracts are used as adjuvant therapies in combination with chemotherapy and radiotherapy, helping to enhance treatment efficacy and accelerate recovery.

At present, many types of fungal polysaccharides have been applied clinically in the treatment of tumors, most of which are β-glucans, as listed in Table 1.

4. Research Background of β-Glucan

β-glucan is a biological response modifier with broad natural sources, low toxicity, minimal side effects, and strong immunoactivity. As a target for industrial development, β-glucan has been studied for many years as a novel material. However, its investigation as an immunoregulatory substance has only begun in recent years. Other emerging research areas—such as cytokines, gene therapy, and tumor vaccines—have also drawn significant attention. Understanding the intrinsic relationships between β-glucan and these new therapeutic fields, and determining whether they can coexist or act synergistically, are urgent questions that require further clarification at the molecular level.

Antitumor activity remains the primary biological indicator of β-glucan’s bioactivity. In addition to in vivo evaluations, efforts are underway to establish a reliable in vitro assay system for accurate assessment.

Because β-glucan is a cell wall component of microorganisms, it can be produced in large quantities through microbial fermentation, a process that offers advantages such as low input, high yield, and industrial scalability. This gives β-glucan tremendous potential for pharmaceutical development, marking it as an important research area within glycobiology with broad prospects for future growth.