title: Evaluating the possible genotoxic, mutagenic and tumor cell proliferation-inhibition effects of a non-anticoagulant, but antithrombotic algal heterofucan.
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.
authors.affiliation: Departamento de Bioquímica, Universidade Federal do Rio Grande do Norte, Av. Senador Salgado Filho, Lagoa Nova, CEP 59072-970, Natal, Brazil.
authors.forename: Jailma
authors.initials: J
authors.lastname: Almeida-Lima
authors.forename: Leandro Silva
authors.initials: LS
authors.lastname: Costa
authors.forename: Naisandra Bezerra
authors.initials: NB
authors.lastname: Silva
authors.forename: Raniere Fagundes
authors.initials: RF
authors.lastname: Melo-Silveira
authors.forename: Fábio Vasconcelos
authors.initials: FV
authors.lastname: Silva
authors.forename: Maria Beatriz Mesquita Cansanção
authors.initials: MB
authors.lastname: Felipe
authors.forename: Silvia Regina Batistuzzo
authors.initials: SR
authors.lastname: Medeiros
authors.forename: Edda Lisboa
authors.initials: EL
authors.lastname: Leite
authors.forename: Hugo Alexandre Oliveira
authors.initials: HA
authors.lastname: Rocha
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004447:Echinodermata / Q000737:chemistry; D005343:Fibrinolytic Agents / Q000494:pharmacology* / Q000633:toxicity*; D005643:Fucose / Q000494:pharmacology; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D009153:Mutagens / Q000494:pharmacology*; D009369:Neoplasms / Q000473:pathology*; D000459:Phaeophyceae / Q000737:chemistry; D011134:Polysaccharides / Q000633:toxicity; D013431:Sulfates / Q000494:pharmacology; D013917:Thrombin / Q000037:antagonists & inhibitors*
chemical_list: D000925:Anticoagulants; D005343:Fibrinolytic Agents; D009153:Mutagens; D011134:Polysaccharides; D013431:Sulfates; D005643:Fucose; D013917:Thrombin