Comparative screening identifies Lanmaoa asiatica polysaccharide as the most potent edible bolete polysaccharide against colorectal cancer with NRF2-GPX4-related redox imbalance

Abstract Colorectal cancer (CRC) is one of the most common malignancies worldwide and remains a major cause of morbidity and mortality. Polysaccharides from edible boletes (BPs) have been reported to possess antitumor activity, but their direct effects on CRC remain poorly understood. In this study, polysaccharides derived from Suillus bovinus (SBP), a Boletus sp. closely related to B. recapitulatus (BP), Lanmaoa asiatica (LMP), and a Boletus sp. closely related to B. edulis (BEP) were evaluated in an AOM/DSS-induced mouse model and CRC cell lines. All four polysaccharides exhibited antitumor activity, with LMP showing the strongest effects. In vitro, LMP markedly inhibited HT-29 cell proliferation by suppressing DNA synthesis and inducing G1-phase cell cycle arrest. Mechanistically, LMP treatment was associated with reduced NRF2 and GPX4 expression, accompanied by ROS accumulation, oxidative stress, and DNA damage, while elevated HO-1 protein levels may reflect a redox-related adaptive response. Our findings suggest that redox-related mechanisms are involved in the antitumor effects of Boletus polysaccharides, and that LMP shows potential as a functional food ingredient for colorectal cancer prevention.