- Polysaccharides have been extensively investigated for their potential as anticancer agents, owing to their natural abundance, biocompatibility, structural diversity, and relatively low toxicity compared to conventional chemotherapeutics.
- Unlike synthetic cytotoxic drugs, many polysaccharides exert anticancer effects through multifaceted mechanisms: directly inhibiting tumor cell proliferation, inducing apoptosis, modulating the immune system, suppressing angiogenesis, and reducing metastasis. Their anticancer activity is strongly linked to their chemical composition, molecular weight, branching, and functional modifications such as sulfation, phosphorylation, and carboxymethylation.
- One of the most well-known classes of anticancer polysaccharides is the β-glucans, commonly found in fungi, yeast, and cereals. These polysaccharides act primarily as biological response modifiers (BRMs) by activating immune cells, including macrophages, dendritic cells, natural killer (NK) cells, and cytotoxic T lymphocytes. β-glucans bind to receptors such as Dectin-1 and complement receptor 3 (CR3), triggering immune signaling cascades that enhance cytokine production (e.g., interleukins, tumor necrosis factor-α, interferons) and stimulate anti-tumor immunity. Notably, fungal polysaccharides such as lentinan (from shiitake mushrooms), schizophyllan (from Schizophyllum commune), and polysaccharide-K (PSK, from Coriolus versicolor) have been clinically tested and, in some countries, approved as adjunct therapies for cancer patients. These compounds do not directly kill tumor cells but enhance host immune defenses, improving survival rates and the effectiveness of chemotherapy or radiotherapy.
- Marine polysaccharides also play an important role in anticancer research. Fucoidan, a sulfated polysaccharide from brown algae, has demonstrated strong anticancer activity through multiple mechanisms, including induction of apoptosis, inhibition of angiogenesis, and suppression of metastasis. Fucoidan activates caspase-dependent pathways, upregulates pro-apoptotic proteins (e.g., Bax), downregulates anti-apoptotic proteins (e.g., Bcl-2), and interferes with signaling pathways like PI3K/Akt and MAPK that are critical for tumor survival. Similarly, carrageenan and laminarin exhibit anticancer potential, though their activity is often enhanced after chemical modification (e.g., sulfation).
- In addition to immune modulation and apoptosis induction, polysaccharides can also affect the tumor microenvironment. They may reduce oxidative stress, inhibit inflammatory pathways that support tumor progression, and alter gut microbiota composition, which indirectly impacts cancer risk and therapy response. Polysaccharides like arabinogalactans and pectins have shown promise in binding to galectin-3, a protein involved in cancer cell adhesion, metastasis, and immune evasion. By blocking galectin-3, these polysaccharides reduce tumor growth and metastatic spread.
- Chemical modifications of polysaccharides have been shown to enhance their anticancer effects. Sulfated, phosphorylated, or carboxymethylated derivatives often display stronger apoptosis-inducing and immune-stimulating activities than their native counterparts. For instance, sulfated chitosan derivatives have been reported to inhibit cancer cell proliferation and angiogenesis more effectively than unmodified chitosan. Moreover, polysaccharides are increasingly being used as drug delivery systems in cancer therapy. Their biodegradability, hydrophilicity, and ability to form nanoparticles or hydrogels allow them to encapsulate and deliver chemotherapeutic drugs in a controlled and targeted manner, reducing side effects.
- From a clinical perspective, polysaccharides are rarely used as stand-alone cancer treatments but serve as complementary or adjuvant therapies. Lentinan and PSK, for example, are prescribed alongside chemotherapy in Japan and China to improve patient survival and quality of life. In Western medicine, polysaccharides are still mostly considered as nutraceuticals or experimental agents, though growing evidence supports their integration into integrative oncology.
