Laminaran from brown alga Dictyota dichotoma and its sulfated derivative as radioprotectors and radiosensitizers in melanoma therapy

Carbohydr Polym. 2019 Feb 15:206:539-547. doi: 10.1016/j.carbpol.2018.11.008. Epub 2018 Nov 10.

Abstract

The laminarans are neutral water-soluble β-D-glucans of brown algae possessing potent immunomodulating, radioprotective, and anticancer activities. The aim of the present study was to investigate in vitro anticancer, radioprotective, and radiosensitizing activities of laminaran from brown alga Dictyota dichotoma and its sulfated derivative. The native and sulfated laminarans by themselves at non-toxic doses possessed significant anticancer activity against melanoma cells. Both polysaccharides protected normal epidermal cells, while only sulfated laminaran was able to sensitize melanoma cells to X-rays irradiation resulting in significant inhibition of cell proliferation, colony formation, and migration of cancer cells. The molecular mechanism of this action was related to the inhibition of MMP-2 and MMP-9 proteinases activity as well as down-regulation of kinases' phosphorylation of ERK1/2 signaling cascade. Taken together, the combination of sulfated derivative of laminaran from D. dichotoma with X-ray may serve as a potential treatment strategy for human melanoma.

Keywords: Laminaran; MAPK; MMPs; Melanoma; Radiation; Sulfated derivative.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Glucans / pharmacology*
  • Humans
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Matrix Metalloproteinase Inhibitors / pharmacology
  • Mice
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Phaeophyceae / chemistry*
  • Polysaccharides / pharmacology*
  • Radiation-Protective Agents / pharmacology*
  • Radiation-Sensitizing Agents / pharmacology*

Substances

  • Antineoplastic Agents
  • Glucans
  • Matrix Metalloproteinase Inhibitors
  • Polysaccharides
  • Radiation-Protective Agents
  • Radiation-Sensitizing Agents
  • laminaran
  • laminarin sulfate
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9