Reactive oxygen species (ROS) produced during intracellular metabolism or triggered by extrinsic factors can promote neoplastic transformation and malignant microenvironment that mediate
tumor development. Oligo-
Fucoidan is a sulfated
polysaccharide isolated from the brown seaweed. Using human THP-1 monocytes and murine Raw264.7 macrophages as well as human HCT116
colorectal cancer cells, primary C6P2-L1
colorectal cancer cells and human MDA-MB231
breast cancer cells, we investigated the effect of Oligo-
Fucoidan on inhibiting M2 macrophage differentiation and its therapeutic potential as a supplement in
chemotherapy and
tumor prevention. We now demonstrate that Oligo-
Fucoidan is an
antioxidant that suppresses intracellular ROS and mitochondrial
superoxide levels in monocytes/macrophages and in aggressive
cancer cells. Comparable to ROS inhibitors (DPI and NAC), Oligo-
Fucoidan directly induced monocyte polarization toward M1-like macrophages and repolarized M2 macrophages into M1 phenotypes. DPI and Oligo-
Fucoidan also cooperatively prevented M2 macrophage invasiveness. Indirectly, M1 polarity was advanced particularly when DPI suppressed ROS generation and supplemented with Oligo-
Fucoidan in the
cancer cells. Moreover,
cisplatin chemoagent polarized monocytes and M0 macrophages toward M2-like phenotypes and Oligo-
Fucoidan supplementation reduced these side effects. Furthermore, Oligo-
Fucoidan promoted cytotoxicity of
cisplatin and antagonized
cisplatin effect on
cancer cells to prevent M2 macrophage differentiation. More importantly, Oligo-
Fucoidan inhibited
tumor progression and M2 macrophage infiltration in tumor microenvironment, thus increasing of anti-
tumor immunity.