Lignosus rhinocerotis polysaccharide induces colon cancer cell apoptosis through the ROS/MAPK pathway and ameliorates gut microbiota imbalance in mice

Colorectal cancer (CRC) as the third largest malignant tumor in the world has seriously threatened human health. Polysaccharides hold significant potential for application in the treatment and prevention of CRC. This study aims to compare the anti-CRC activity of Lignosus rhinocerotis polysaccharide (LRP) and degraded LRP (DLRP), and elucidate the mechanism of their anti-CRC effects. Results showed that the anti-CRC effect of DLRP (IC50, 55.44 µg/mL) was superior to that of LRP (IC50, 220.92µg/mL). LRP and DLRP can cause cycle arrest in HT-29 cells at the G2/M phase, and simultaneously promote the accumulation of ROS in cells, thereby leading to cell apoptosis. Moreover, the mitogen-activated protein kinase signaling pathway was involved in apoptosis and cell cycle arrest in HT-29 cells. In vivo experiment revealed that DLRP effectively ameliorated clinicopathologic symptoms of CRC mice and attenuated inflammatory responses, and also increased concentrations of acetic, propionic, and butyric acid in feces. Apart from significantly inhibiting the growth of harmful bacteria such as Helicobacter and Mucispirillum, DLRP also promoted the proliferation of beneficial bacteria such as Parabacteroides, Muribaculum, and Akkermansia. Overall, DLRP is expected to be a potential drug for the treatment of CRC.