Sargassum henslowianum polysaccharides induce apoptosis of prostate cancer associated macrophages via the CD206-ERK-ROS pathway.

Tumor-associated macrophages (TAMs) are a predominant immunosuppressive cell type within the tumor microenvironment. Whether polysaccharides from Sargassum henslowianum C. Ag. (SH) exert anti-tumor effects by modulating TAMs remains under investigation. In this study, we isolated and characterized a uniform sulfated polysaccharide, SHA1P-2, from SH, with a molecular weight of 68,000 g/mol. Monosaccharide composition analysis revealed that fucose and galactose were the predominant components, with minor amounts of xylose and mannose. RM1-Raw264.7 cells, simulating TAMs, were induced by culturing Raw264.7 cells in the supernatant of prostate cancer RM1 cells, and their effects on T-cell proliferation were assessed. Unlike Raw264.7 cells, RM1-Raw264.7 cells significantly suppressed concanavalin A-induced T-cell proliferation, a suppression alleviated by SHA1P-2 treatment. Interestingly, SHA1P-2 did not induce apoptosis in Raw264.7 cells but effectively triggered apoptosis in RM1-Raw264.7 cells. The apoptotic mechanism was mediated via the upregulation of CD206 in TAMs, as evidenced by reduced apoptosis and reactive oxygen species (ROS) levels when CD206 was knocked down or p-ERK was inhibited in TAMs. These findings demonstrate that SHA1P-2 promotes TAM apoptosis via the CD206-ERK-ROS axis, indicating that elevated ROS levels serve as a key trigger for TAM apoptosis, thereby presenting a novel strategy for TAM-based anti-tumor therapies.