Overcharged lipid metabolism in mechanisms of antitumor by Tremella fuciformis-derived polysaccharide

Tremella fuciformis-derived polysaccharide (TFP) is a natural macromolecular compound that is well known for whitening skin, as well as for its ability to regulate lipids and immunity. However, its mechanism of action is not clear. In the present study, B16 cells treated with TFP were inoculated subcutaneously in the right flank of C57BL/6 mice to explore the effect of TFP on melanoma in vivo. Western blotting, immunohistochemistry, immunofluorescence staining and transcription analysis of tumors were utilized to assess the expression of key molecules in production of melanin, lipid metabolism and immunity. It was found that TFP promoted B16 cell apoptosis and induced G(2)/M cell cycle arrest, which was associated with activation of cell cycle-related pathways. TFP induced the expression of glucose transporter type 4 and CD36, thus resulting in an increase in the uptake of lipids, which markedly suppressed sterol regulatory element-binding transcription factor 1 and phosphorylated-AMP-activated protein kinase expression; increased the number of lipids in the cell membrane, endoplasmic reticulum and nucleus; and induced the RNA expression of molecules related to lipid metabolism, as revealed by RNA-sequencing in vivo. Increased lipid binding, upregulated lipid storage, and elevated triglyceride and lipid catabolism resulted in disruption of cell volume homeostasis and activated innate immune response, thus inhibiting melanoma development and progression. These data revealed a novel molecular mechanism involved in the antitumor effect of TFP via lipid metabolism.