Structural Characterization and Anti-Tumor Activity of a Polysaccharide from Laetiporus sulphureus in A549 Cells

While numerous bioactive polysaccharides have been identified from mushrooms, their mechanisms of action, particularly through the induction of oxidative stress in tumor cells, remain underexplored. This study isolates a novel polysaccharide, LSPS2, derived from Laetiporus sulphureus, followed by the elucidation of its distinctive structural features and specific antitumor activity in A549 lung carcinoma cells. LSPS2 was composed primarily of glucose (88.1%) and minor amounts of mannose (8.0%) and galactose (3.9%). Methylation and one-dimensional/two-dimensional nuclear magnetic resonance (1D/2D NMR) analysis results indicated that LSPS2 was composed of (1→3)-linked-D-β-glucopyran residues and (1→4)-linked-D-α-glucopyran residues as the main chain. The side chains were connected to O-6 and O-3 of glucopyranose (Glcp) residues with terminal Glcp. It differs from previous reports on L. sulphureus polysaccharides. Functionally, LSPS2 markedly suppressed A549 cell viability in a manner that depended on both exposure duration and concentration. LSPS2 upregulated malondialdehyde (MDA) and downregulated reduced glutathione (GSH), demonstrating that LSPS2 induces oxidative stress in A549 cells. The results of superoxide dismutase (SOD) activity assays further indicated that LSPS2 downregulates SOD activity, which may be the mechanism by which LSPS2 induces oxidative stress and, consequently, apoptosis in A549 cells. This targeted downregulation of a key antioxidant enzyme highlights a potential pathway for polysaccharide-induced tumor cell death. Our findings not only identify LSPS2 as a structurally distinct biopolymer but also elucidate its mode of action, underscoring its prospective application in tumor therapy and functional foods, warranting further investigation.