Carboxymethylated and sulfated Cyclocarya paliurus polysaccharides inhibited colon cancer cells growth via PI3K/AKT-MAPKs/NF- κ B pathways and immunomodulation

Our previous research revealed that carboxymethylation modification (CM-CP) and sulfation modification (S-CP) could enhance the antitumor activity of Cyclocarya paliurus polysaccharides (CP), however, the antitumor mechanisms of CM-CP and S -CP are not fully clarified and remain largely unexplored. The aims of the present study were to investigate the dual anti -tumor function of CM-CP and S -CP in inhibiting cancer cells and activating macrophages to exert immunomodulation. Results revealed that CM-CP and S -CP preferentially inhibited the proliferation of colon cancer CT -26 cells in dose -dependent and time -dependent ways, without toxicity to normal cell lines. Flow cytometry values further established that CM-CP and S -CP interventions elicited acidification in the cells, arrested the cell cycle in S stage, raised the amount of reactive oxygen species and activated oxidative stress. CM-CP and S -CP treatment elicited the depolarization of mitochondrial membranous potentials and Ca 2 + superload, and disrupted the equilibrium of Na + /K + -ATPase and Ca 2 + -ATPase. Simultaneously, apoptotic proteins expression assays revealed that CM-CP and S -CP promoted CT -26 cell apoptosis through PI3K/ AKT-MAPKs/NF- kappa B signal pathways. In parallel, CM-CP and S -CP dramatically promoted the proliferation and secretory activity (TNF- alpha and NO) of RAW264.7 cells. Co -culture of cancer cells with CM-CP and S -CP-stimulated macrophage supernatants resulted in more pronounced suppression of cancer cell viability. These findings demonstrated that CM-CP and CM-CP not only inhibit cancer cell growth directly, but also activate macrophages to exert immunomodulatory effects to suppress cancer cells. Furthermore, CM-CP and CM-CP make a contribution to the development of potential functional foods or supplements for the prevention or treatments of colorectal cancer.