Fucoidan Prevents M2 Macrophage Differentiation and HCT116 Tumor Progression in Mice

  • Date: 2021-09-30
  • Update: 2021-09-30
  • Source: 國家衛生研究院
  • Views: 468

Fucoidan Prevents M2 Macrophage Differentiation and HCT116 Tumor Progression in Mice


NHRI scientists found fucoidan inhibited HCT116 tumor progression in xenograft mice and M2 macrophage infiltration in the tumor microenvironment, thus increasing anti-tumor immunity


September 26, 2021


Cancers have been the leading causes of death in Taiwan for decades. More than 50,000 people in Taiwan died of cancer last year, accounting for 29% of the total deaths, according to statistics from the Ministry of Health and Welfare’s Health Promotion Administration. Therefore, it is urgent to identify more effective therapeutic strategies or new combinatorial therapies.


The tumor microenvironment has been seen as a promising target for cancer treatment due to its decisive roles in tumor heterogeneity, dissemination, and immune evasion. Tumors often exhibit higher basal levels of reactive oxygen species (ROS) with altered redox machinery than normal cells. ROS during intracellular metabolism or triggered by extrinsic factors can either promote or restrict tumorigenicity; and higher mitochondrial ROS is actually required for neoplastic cell transformation, cancer survival and metastasis, and reprogramming a malignant microenvironment.


Fucoidan is a sulfated polysaccharide isolated from brown seaweed. Using human THP-1 monocytes and murine Raw264.7 macrophages, as well as human HCT116 colorectal cancer cells, primary C6P2-L1 primary colorectal cancer cells, and human MDA-MB231 breast cancer cells, a team led by Dr. Hsin-Ling Hsu of the National Health Research Institutes’ Institute of Molecular and Genomic Medicine investigated the effect of fucoidan on inhibiting M2 macrophage differentiation and its therapeutic potential as a supplement in chemotherapy and tumor prevention. Moreover, Dr. Hsu’s team explored the possibility that antioxidants supplemented with fucoidan may enhance the tumor-suppressive and immuno-supportive characteristics of macrophages, which may in turn benefit cancer therapeutics.


Research by Dr. Hsu’s team demonstrated the following:

  • 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), fucoidan directly induced monocyte polarization toward M1-like macrophages and repolarized M2 macrophages into M1 phenotypes.
  • DPI and fucoidan also cooperatively prevented M2 macrophage invasiveness. Indirectly, M1 polarity was advanced, particularly when DPI suppressed ROS generation and was supplemented with fucoidan in the cancer cells.
  • The chemoagent cisplatin directly polarized monocytes and M0 macrophages toward M2-like phenotypes, and fucoidan supplementation reduced these side effects.
  • Fucoidan promoted the cytotoxicity of cisplatin and antagonized cisplatin’s effect on cancer cells to prevent M2 macrophage differentiation.

The findings of the study were published in Cancers in February 2020.

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