Sulfated polysaccharides of Laetiporus sulphureus fruiting bodies exhibit anti-breast cancer activity through cell cycle arrest, apoptosis induction, and inhibiting cell migration.

ETHNOPHARMACOLOGICAL RELEVANCE: Laetiporus sulphureus has long been used as an edible and medicinal mushroom in Asia, America, and Europe. Its fruiting bodies are widely used in folk medicine for treating cancer, gastric diseases, cough, and rheumatism. Polysaccharides are an important bioactive component of mushrooms. In nature, sulfated polysaccharides have never been reported in mushrooms. Furthermore, there is no information on differences in physicochemical properties and anti-breast cancer activities between polysaccharides (PS) and sulfated polysaccharides (SPS) of L. sulphureus. AIM OF THE STUDY: This study aimed to investigate the physicochemical properties of PS and SPS isolated from fruiting bodies of L. sulphureus and examine their anti-proliferative effects and mechanism(s) of action on MDA-MB-231 breast cancer cells. METHODS: Polysaccharides (PS) were isolated using hot water and ethanol precipitation methods. Sulfated polysaccharides (SPS) were isolated by the papain-assisted hydrolysis method. Physicochemical properties comprising sugar, protein, uronic acid, and sulfate contents, and molecular weight, monosaccharide composition, and structural conformation were analyzed on PS and SPS. In the anti-cancer study, a triple-negative breast cancer cell line (MDA-MB-231) and a normal human mammary epithelial cell line (H184B5F5/M10) were used to evaluate the anti-proliferative activity of PS and SPS, and their mechanism(s) of action. RESULTS: The results showed that SPS, which had higher sulfate and protein contents and diversified monosaccharide composition, exhibited more potent anti-proliferative activity against MDA-MB-231 cells than PS. Furthermore, it had a selective cytotoxic effect on breast cancer cells but not the normal cells. SPS induced cell cycle arrest at G0/G1 phase via down-regulating CDK4 and cyclin D1 and up-regulating p21 protein expression. Breast cancer cell apoptosis was not observed until 72 h after SPS treatment. In addition, SPS also markedly inhibited breast cancer cell migration. CONCLUSION: This study demonstrates that SPS exhibited selective cytotoxicity and was more potent than PS in inhibiting MDA-MB-231 cell proliferation. The contents of sulfate and protein, and monosaccharide composition could be the main factors affecting the anti-breast cancer activity of L. sulphureus SPS.

SPS, a sulfated galactoglucan of Laetiporus sulphureus, exhibited anti-inflammatory activities.

Laetiporus sulphureus is an edible and medicinal mushroom. A sulfated galactoglucan (SPS) was isolated by the papain method. Polysaccharides (PS) were isolated by hot water and ethanol precipitation. The medium molecular weight SPS of 100 to 1000 kDa accounted for over half of the SPS mixture. Fucose, galactose, glucose, and mannose were the major monosaccharides in SPS and PS. The amount of sulfate in SPS was 1.09 mmol/g. SPS showed inhibition of tumor necrosis factor-α (TNF-α) release and reversed IκB degradation in LPS-induced RAW264.7 macrophages. The suppression of TNF-α secretion by SPS was through inhibiting the phosphorylation of AKT/extracellular signal-regulated kinases (ERK), p38, and c-Jun N-terminal kinase (JNK). A purified SPS, named SPS-3, was proven to inhibit the LPS-induced phosphorylation of AKT, ERK, and p-38 in RAW264.7 cells. The suppression of interleukin 6 (IL-6) and transforming growth factor beta (TGFß) secretion by PS was through inhibiting LPS-induced phosphorylation of p-38 and TGF-ß receptor II (TGFRII) signaling pathways. This study demonstrates that the isolated SPS and PS from L. sulphureus possessed good anti-inflammatory activity for dietary supplements and functional food.

Synergistic anti-inflammatory effects of different polysaccharide components from Xylaria nigripes.

Nondigestible polysaccharides are essential nutrients, which are also important bioactive constituents of mushrooms. This study aimed to investigate the physicochemical properties and anti-inflammatory effects of different polysaccharide components of Xylaria nigripes in lipopolysaccharides (LPS)-induced RAW264.7 macrophages. Results showed that X. nigripes nondigestible polysaccharide (XN) possessed a molecular weight of 910.7 kDa and mainly composed of glucose; it effectively suppressed NO, TNF-α, and IL-6 production. Based on molecular weight, two bioactive polysaccharide components (F1 and F2) were isolated from XN. F1 was a glucan with high molecular weight (885.2 kDa), whereas F2 was a low molecular weight heteropolysaccharide (24.5 kDa) composing of glucose, mannose, and galactose. F1 showed stronger inhibitory effects on NO, TNF-α, and IL-6 production than F2, however, its inhibitory effects were weaker than XN. Further analysis demonstrated that the combined treatment of F1 and F2 exhibited anti-inflammatory activity as good as XN, and they possessed synergistic effects on inhibiting pro-inflammatory mediator production. PRACTICAL APPLICATIONS: Polysaccharides are essential nutrients, and are major bioactive constituents of mushrooms. This study isolated two bioactive polysaccharide components from Xylaria nigripes, namely F1 and F2. F1 was a high molecular weight glucan, whereas F2 was a low molecular weight heteropolysaccharide. F1 showed stronger anti-inflammatory activity than F2, but was weaker than their combined treatment (F1 + F2). Different polysaccharide components were shown to possess synergistic anti-inflammatory effects, suggesting their importance in the formulation of polysaccharide-based products.