Characterization and antitumor activities of polysaccharides derived from Inonotus sanghuang against cancers of the liver and lungs.

To evaluate the mechanism underlying the antitumor activity of polysaccharides derived from Inonotus sanghuang and assess the impact of fractionation on these activities, crude polysaccharides were extracted and separated into two fractions:an ethanol-precipitated crude polysaccharide (ESP) and a bioactive water-soluble polysaccharide (DSP). Both ESP and DSP displayed distinct molecular-size distributions, and monosaccharide analysis indicated that these fractions were heteropolysaccharides composed of neutral sugars, significant amounts of uronic acids, and amino sugars. The antitumor activities of ESP and DSP were evaluated in vitro using hepatocellular carcinoma (HepG2) and lung cancer (A549) cell lines, as well as their corresponding xenograft models. Both ESP and DSP effectively inhibited tumor cell proliferation and migration, while inducing G1-phase cell cycle arrest. Importantly, neither fraction affected the viability of non-tumor cells (293 T and THLE-2). Mechanistic investigations indicated that ESP and DSP elicited mitochondria-related stress responses, along with alterations in cell death-associated proteins and signaling pathways. Notably, ESP and DSP suppressed tumor growth in vivo without evident systemic toxicity based on an evaluation of the overall condition of the animals and histology of major organs. In conclusion, the fractionation of polysaccharides from Inonotus sanghuang resulted in the enrichment of active polysaccharides, thereby enhancing their antitumor efficacy and selectivity. These results highlight the therapeutic potential of Inonotus sanghuang polysaccharides against liver and lung cancers, supporting their further development as promising anticancer agents.