title: Interaction effects of enniatin B, deoxinivalenol and alternariol in Caco-2 cells.
abstract: Enniatin B (ENN B), deoxinivalenol (DON) and alternariol (AOH) are secondary metabolites of filamentous fungi. These mycotoxins are contaminants of vegetables and cereals. They are cytotoxic and their effects are enhanced by their mixtures. The objectives of this study were to compare the cytotoxicity of ENN B, DON and AOH alone or in combination in human adenocarcinoma (Caco-2) cells and to evaluate the type of interactions of mycotoxin mixtures by the isobologram analysis. Cells were treated with concentrations ranging from 1.85 to 90μM (AOH) and from 0.312 to 10μM (for ENN B and DON), individually and in combination of two and three mycotoxins (from 1.85 to 30μM for AOH and from 0.312 to 5μM for ENN B and DON). The relation ratios between the mixtures DON+ENN B was 1:1; AOH+DON and ENN B+AOH was 1:6, and for the tertiary combination DON, ENN B and AOH 1:1:6. The IC50 value of ENN B and DON were 3.87 and 5.54μM, respectively. No IC50 values were obtained for the AOH at any time tested in Caco-2 cells. With the isobologram the type of interaction between mycotoxin was evaluated. Synergistic, antagonistic and addictive effect was observed for the combination studied depending on the concentration affected. Mycotoxins combinations reduce cellular viability in the following increasing order: (DON+ENN B)>(ENN B+AOH)>(DON+AOH)>(DON+AOH+ENN B).
authors.affiliation: Laboratory of Food Chemistry and Toxicology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés s/n, 46100 Burjassot, Valencia, Spain. Electronic address: celia.fernandez-blanco@uv.es.
authors.forename: Celia
authors.initials: C
authors.lastname: Fernández-Blanco
authors.affiliation: Laboratory of Food Chemistry and Toxicology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés s/n, 46100 Burjassot, Valencia, Spain.
authors.forename: Guillermina
authors.initials: G
authors.lastname: Font
authors.affiliation: Laboratory of Food Chemistry and Toxicology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés s/n, 46100 Burjassot, Valencia, Spain.
authors.forename: Maria-Jose
authors.initials: MJ
authors.lastname: Ruiz
mesh_terms: D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D047630:Depsipeptides / Q000494:pharmacology*; D004347:Drug Interactions; D005506:Food Contamination; D006801:Humans; D007783:Lactones / Q000633:toxicity*; D009183:Mycotoxins / Q000633:toxicity*; D014255:Trichothecenes / Q000633:toxicity*
chemical_list: D047630:Depsipeptides; D007783:Lactones; D009183:Mycotoxins; D014255:Trichothecenes; C100264:enniatins; C007262:deoxynivalenol; C005197:alternariol
keywords: Caco-2 cells; Cytotoxicity; Interactions; Isobolograms; Mycotoxins