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A sulfated polysaccharide low-molecular-weight fucoidan, with potential antioxidant, anti-inflammatory, antiproliferative, anti-angiogenic and pro-apoptotic activities. Upon administration of oligo-fucoidan, this agent seems to exert numerous effects through various mechanisms of action, some of which remain to be fully elucidated. Oligo-fucoidan induces cell cycle arrest, activates caspases, induces apoptosis, and inhibits tumor cell proliferation in susceptible tumor cells. It also increases the expression of tumor suppressors, such as p53, while decreasing levels of certain tumor promoters. Oligo-fucoidan also promotes the degradation of transforming growth factor-beta (TGFb) receptor and the inhibition of epithelial-mesenchymal transition (EMT). It prevents tumor progression, alters tumor microenvironment (TME) and decreases the tumor-promoting M2 macrophages in the TME. Oligo-fucoidan has anti-inflammatory effects that suppress the expression of nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 and monocyte chemoattractant protein-1 (MCP-1/CCL2), and decrease the production of certain pro-inflammatory cytokines, such as interleukin-1beta (IL-1b) and tumor necrosis factor (TNF)-alpha (TNFa). This agent may also suppress angiogenic activity by inhibiting vascular endothelial growth factor (VEGF) receptor expression and VEGF-induced endothelial cell proliferation. As an antioxidant, this agent protects cells against oxidative stress by scavenging superoxide radicals and induces the expression of the anti-oxidant nuclear factor erythroid-2-related factor 2 and that of its target gene, superoxide dismutase; and prevents reactive oxidative species (ROS) generation in cancer cells and ROS release into the TME. Fucoidan also has immune-modulatory effects and enhances the proliferation of natural killer (NKs) cells and cytotoxic T-cells (CTLs).
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