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Open AccessArticle

Oligo-Fucoidan Prevents M2 Macrophage Differentiation and HCT116 Tumor Progression

1
Institute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli 35053, Taiwan
2
National Taiwan Ocean University, Keelung 20224, Taiwan
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(2), 421; https://doi.org/10.3390/cancers12020421
Received: 18 January 2020 / Accepted: 10 February 2020 / Published: 12 February 2020
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. View Full-Text
Keywords: Oligo-Fucoidan; antioxidant; cisplatin; ROS; M1/M2 macrophages; tumor progression Oligo-Fucoidan; antioxidant; cisplatin; ROS; M1/M2 macrophages; tumor progression
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Chen, L.-M.; Tseng, H.-Y.; Chen, Y.-A.; Al Haq, A.T.; Hwang, P.-A.; Hsu, H.-L. Oligo-Fucoidan Prevents M2 Macrophage Differentiation and HCT116 Tumor Progression. Cancers 2020, 12, 421.

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