Growth inhibition of hepatocellular carcinoma by the polysaccharide–protein complex from <scp> <i>Inonotus hispidus</i> </scp> mycelia and the mechanisms

Abstract BACKGROUND Polysaccharide–protein (PSP) complexes derived from edible fungi are promising candidates against tumors, offering substantial efficacy with minimal side effects. This study aimed to isolate a PSP from the cultivated mycelia of the edible fungus Inonotus hispidus and evaluate its antitumor potential. RESULTS Through activity‐guided fractionation, a highly active fraction, PSP‐1, was attained and characterized as a PSP complex containing 644.8 g kg −1 total sugar and 288.9 g kg −1 protein, with an average molecular weight of 327 kDa. The polysaccharide portion of PSP‐1 was composed of glucose, mannose, galactose, and fucose at a molar ratio of 4.90:2.55:3.35:1.00, and the protein part was composed dominantly of glutamic acid, methionine, and aspartic acid. In vivo , PSP‐1 showed a significant tumor inhibition rate of 36.9 ± 2.3% at a low dose of 100 mg kg −1 in a hepatocellular carcinoma model and doubled the antitumor efficacy of cyclophosphamide. In HepG2 cancer cell culture, PSP‐1 significantly inhibited cell proliferation with an half‐maximal inhibitory concentration (IC 50 ) value of 87.9 μg mL −1 . PSP‐1 induced apoptosis via cell cycle arrest through a mitochondria‐mediated Caspase‐dependent pathway. CONCLUSION The findings suggest that the I. hispidus mycelium‐derived PSP complex is a promising component in functional foods to prevent the occurrence and inhibit the development of liver tumors, either alone or in combination with chemotherapy drugs. © 2026 Society of Chemical Industry.