title: Anisakis pegreffii (Nematoda: Anisakidae) products modulate oxidative stress and apoptosis-related biomarkers in human cell lines.
abstract: In countries with elevated prevalence of zoonotic anisakiasis and high awareness of this parasitosis, a considerable number of cases that associate Anisakis sp. (Nematoda, Anisakidae) and different bowel carcinomas have been described. Although neoplasia and embedded larvae were observed sharing the common site affected by chronic inflammation, no association between the nematode and malignancy were directly proved. Similarly, no data are available about the effect of secretory and excretory products of infecting larvae at the host's cellular level, except in respect to allergenic interaction.
  
  
  
  To test the mechanisms by which human non-immune cells respond to the larvae, we exposed the fibroblast cell line HS-68 to two Anisakis products (ES, excretory/secretory products; and EC, crude extract) and evaluated molecular markers related to stress response, oxidative stress, inflammation and apoptosis, such as p53, HSP70, TNF-α, c-jun and c-fos, employing cell viability assay, spectrophotometry, immunoblotting and qPCR.
  
  
  
  Both Anisakis products led to increased production of reactive oxygen species (ROS), especially in EC-treated cells. While the ES treatment induces activation of kinases suggesting inflammation and cell proliferation (or inhibition of apoptosis), in EC-treated cells, other signaling pathways indicate the inhibition of apoptosis, marked by strong upregulation of Hsp70. Elevated induction of p53 in fibroblasts treated by both Anisakis products, suggests a significantly negative effect on the host DNA.
  
  
  
  This study shows that in vitro cell response to Anisakis products can result in at least two different scenarios, which in both cases lead to inflammation and DNA damage. Although these preliminary results are far from proving a relationship between the parasite and cancer, they are the first to support the existence of conditions where such changes are feasible.
authors.affiliation: Dipartimento di Scienze della Terra e del Mare DiSTeM, Università degli Studi di Palermo, Laboratorio di Biochimica Marina ed Ecotossicologia, Via G. Barlotta 4, 91100, Trapani, Italy.
authors.forename: Concetta Maria
authors.initials: CM
authors.lastname: Messina
authors.affiliation: Dipartimento di Scienze della Terra e del Mare DiSTeM, Università degli Studi di Palermo, Laboratorio di Biochimica Marina ed Ecotossicologia, Via G. Barlotta 4, 91100, Trapani, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Pizzo
authors.affiliation: Dipartimento di Scienze della Terra e del Mare DiSTeM, Università degli Studi di Palermo, Laboratorio di Biochimica Marina ed Ecotossicologia, Via G. Barlotta 4, 91100, Trapani, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Santulli
authors.affiliation: Institute of Oceanography and Fisheries, Laboratory of Aquaculture, POBox 500, 21000, Split, Croatia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Bušelić
authors.affiliation: University of Split, Faculty of Natural Sciences, Teslina 12, 21000, Split, Croatia.
authors.forename: Mate
authors.initials: M
authors.lastname: Boban
authors.affiliation: University of Split, Faculty of Natural Sciences, Teslina 12, 21000, Split, Croatia.
authors.forename: Stjepan
authors.initials: S
authors.lastname: Orhanović
authors.affiliation: Institute of Oceanography and Fisheries, Laboratory of Aquaculture, POBox 500, 21000, Split, Croatia. mladineo@izor.hr.
authors.forename: Ivona
authors.initials: I
authors.lastname: Mladineo
mesh_terms: D000818:Animals; D017163:Anisakis / Q000737:chemistry*; D017209:Apoptosis; D001688:Biological Products / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007814:Larva / Q000737:chemistry; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D001688:Biological Products; D015415:Biomarkers; D018836:Inflammation Mediators; D017382:Reactive Oxygen Species
keywords: Anisakis pegreffii; Apoptosis; Fibroblast cell lines HS-68; Inflammation; Oxidative stress