Prophylactic administration of fucoidan represses cancer metastasis by inhibiting vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) in Lewis tumor-bearing mice

Mar Drugs. 2015 Apr 3;13(4):1882-900. doi: 10.3390/md13041882.


Fucoidan, a heparin-like sulfated polysaccharide, is rich in brown algae. It has a wide assortment of protective activities against cancer, for example, induction of hepatocellular carcinoma senescence, induction of human breast and colon carcinoma apoptosis, and impediment of lung cancer cells migration and invasion. However, the anti-metastatic mechanism that fucoidan exploits remains elusive. In this report, we explored the effects of fucoidan on cachectic symptoms, tumor development, lung carcinoma cell spreading and proliferation, as well as expression of metastasis-associated proteins in the Lewis lung carcinoma (LLC) cells-inoculated mice model. We discovered that administration of fucoidan has prophylactic effects on mitigation of cachectic body weight loss and improvement of lung masses in tumor-inoculated mice. These desired effects are attributed to inhibition of LLC spreading and proliferation in lung tissues. Fucoidan also down-regulates expression of matrix metalloproteinases (MMPs), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and vascular endothelial growth factor (VEGF). Moreover, the tumor-bearing mice supplemented with fucoidan indeed benefit from an ensemble of the chemo-phylacticity. The fact is that fucoidan significantly decreases viability, migration, invasion, and MMPs activities of LLC cells. In summary, fucoidan is suitable to act as a chemo-preventative agent for minimizing cachectic symptoms as well as inhibiting lung carcinoma metastasis through down-regulating metastatic factors VEGF and MMPs.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Cachexia / etiology
  • Cachexia / prevention & control
  • Carcinoma, Lewis Lung / drug therapy*
  • Carcinoma, Lewis Lung / metabolism
  • Carcinoma, Lewis Lung / pathology
  • Carcinoma, Lewis Lung / secondary
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Matrix Metalloproteinase Inhibitors / administration & dosage
  • Matrix Metalloproteinase Inhibitors / pharmacology
  • Matrix Metalloproteinase Inhibitors / therapeutic use*
  • Matrix Metalloproteinases / chemistry
  • Matrix Metalloproteinases / metabolism*
  • Mice, Inbred C57BL
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism
  • Neoplasm Invasiveness / prevention & control
  • Neoplasm Proteins / antagonists & inhibitors*
  • Neoplasm Proteins / metabolism
  • Phaeophyta / chemistry
  • Polysaccharides / administration & dosage
  • Polysaccharides / pharmacology
  • Polysaccharides / therapeutic use*
  • Seaweed / chemistry
  • Tumor Burden / drug effects
  • Vascular Endothelial Growth Factors / antagonists & inhibitors*
  • Vascular Endothelial Growth Factors / metabolism


  • Antineoplastic Agents
  • Matrix Metalloproteinase Inhibitors
  • NF-kappa B
  • Neoplasm Proteins
  • Polysaccharides
  • Vascular Endothelial Growth Factors
  • fucoidan
  • Matrix Metalloproteinases