Fucoidan Does Not Exert Anti-Tumorigenic Effects on Uveal Melanoma Cell Lines

Mar Drugs. 2017 Jun 22;15(7):193. doi: 10.3390/md15070193.

Abstract

Background: The polysaccharide fucoidan is widely investigated as an anti-cancer agent. Here, we tested the effect of fucoidan on uveal melanoma cell lines.

Methods: The effect of 100 µM fucoidan was investigated on five cell lines (92.1, Mel270 OMM1, OMM2.3, OMM2.5) and of 1 µg/mL-1 mg/mL fucoidan in two cell lines (OMM1, OMM2.3). Cell proliferation and viability were investigated with a WST-1 assay, migration in a wound healing (scratch) assay. Vascular Endothelial Growth Factor (VEGF) was measured in ELISA. Angiogenesis was evaluated in co-cultures with endothelial cells. Cell toxicity was induced by hydrogen-peroxide. Protein expression (Akt, ERK1/2, Bcl-2, Bax) was investigated in Western blot.

Results: Fucoidan increased proliferation in two and reduced it in one cell line. Migration was reduced in three cell lines. The effect of fucoidan on VEGF was cell type and concentration dependent. In endothelial co-culture with 92.1, fucoidan significantly increased tubular structures. Moreover, fucoidan significantly protected all tested uveal melanoma cell lines from hydrogen-peroxide induced cell death. Under oxidative stress, fucoidan did not alter the expression of Bcl-2, Bax or ERK1/2, while inducing Akt expression in 92.1 cells but not in any other cell line.

Conclusion: Fucoidan did not show anti-tumorigenic effects but displayed protective and pro-angiogenic properties, rendering fucoidan unsuitable as a potential new drug for the treatment of uveal melanoma.

Keywords: VEGF; angiogenesis; fucoidan; oxidative stress; uveal melanoma.

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology*
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Coculture Techniques
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Melanoma / drug therapy*
  • Melanoma / pathology
  • Neovascularization, Pathologic / drug therapy
  • Oxidative Stress / physiology
  • Polysaccharides / administration & dosage
  • Polysaccharides / pharmacology*
  • Uveal Neoplasms / drug therapy*
  • Uveal Neoplasms / pathology
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Antineoplastic Agents
  • Polysaccharides
  • Vascular Endothelial Growth Factor A
  • fucoidan

Supplementary concepts

  • Uveal melanoma