Evaluating the possible genotoxic, mutagenic and tumor cell proliferation-inhibition effects of a non-anticoagulant, but antithrombotic algal heterofucan

J Appl Toxicol. 2010 Oct;30(7):708-15. doi: 10.1002/jat.1547.

Abstract

Fucan is a term used to denominate a family of sulfated polysaccharides rich in L-fucose. They are extracted mainly from brown seaweeds and echinoderms. The brown seaweed Spatoglossum schröederi (Dictyotaceae) synthesizes three heterofucans named A, B and C. Our research group purified a non-anticoagulant heterofucan (fucan A) which displays antithrombotic activity in vivo. However, its in vitro toxicity has yet to be determined. This work presents the evaluation of the potential cytotoxicity, mutagenicity and genotoxicity of this fucan. After 48 h incubation fucan A cytotoxicity was determinate using MTT assay. Tumor-cell (HeLa, PC3, PANC, HL60) proliferation was inhibited 2.0-43.7%; at 0.05-1 mg ml⁻¹ of the heterofucan, the 3T3 non-tumor cell line proliferation was also inhibited (3.3-22.0%). On the other hand, the CHO tumorigenic and RAW non-tumor cell lines proliferation were not affected by this molecule (0.05-1 mg ml⁻¹). We observed no mutagenic activity in Salmonella reversion assay when bacterial strains TA97a, TA98, TA100 and TA102 (with and without S9) were used.Comet assay showed that fucan A had no genotoxic effect (from 20 to 1000 mg ml⁻¹) on CHO cells. In conclusion, this study indicates that the S. schröederi fucan A was not found to be genotoxic or mutagenic compound; thus it could be used in new antithrombotic drug development.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticoagulants / pharmacology
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • DNA Damage*
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Echinodermata / chemistry
  • Fibrinolytic Agents / pharmacology*
  • Fibrinolytic Agents / toxicity*
  • Fucose / pharmacology
  • HL-60 Cells
  • HeLa Cells
  • Humans
  • Mutagens / pharmacology*
  • Neoplasms / pathology*
  • Phaeophyceae / chemistry
  • Polysaccharides / toxicity
  • Sulfates / pharmacology
  • Thrombin / antagonists & inhibitors*

Substances

  • Anticoagulants
  • Fibrinolytic Agents
  • Mutagens
  • Polysaccharides
  • Sulfates
  • Fucose
  • Thrombin