title: 4-Nonylphenol reduces cell viability and induces apoptosis and ER-stress in a human epithelial intestinal cell line.
abstract: 4-Nonylphenol is a widely diffused and stable environmental contaminant, originating from the degradation of alkyl phenol ethoxylates, common surfactants employed in several industrial applications. Due to its hydrophobic nature, 4-nonylphenol can easily accumulate in living organisms, including humans, where it displays a wide range of toxic effects. Since the gastrointestinal tract represents the main route by which 4-nonylphenol enters the body, the intestine may be one of the first organs to be damaged by chronic exposure to this pollutant through the diet. In the present study, we investigated the effects of 4-nonylphenol on a human intestinal epithelial cell line (Caco-2 cells). We demonstrated that 4-nonylphenol was cytotoxic to cells, as revealed by a decrease of the cell number and the decrement of mitochondrial functionality after 24 h of treatment. 4-Nonylphenol also reduced the number of cells entering into S-phase and interfered with epidermal growth factor signalling, with consequent negative effects on cell survival. In addition, 4-nonylphenol induced apoptosis, involving the activation of caspase-3, and triggered an endoplasmic reticulum-stress response, as revealed by over-expression of GRP78 (78 kDa glucose-regulated protein) and activation of XBP1 (X-box binding protein-1). Together, these findings support the hypothesis that prolonged exposure to 4-nonylphenol through the diet may lead to local damage at the level of intestinal mucosa, with potentially negative consequences for intestinal homeostasis and functionality.
authors.affiliation: Dept. of Chemistry and Biology, University of Salerno, via Giovanni Paolo II, 132, 84084 Fisciano, SA, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Lepretti
authors.affiliation: Dept. of Chemistry and Biology, University of Salerno, via Giovanni Paolo II, 132, 84084 Fisciano, SA, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Paolella
authors.affiliation: Dept. of Chemistry and Biology, University of Salerno, via Giovanni Paolo II, 132, 84084 Fisciano, SA, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Giordano
authors.affiliation: Dept. of Chemistry and Biology, University of Salerno, via Giovanni Paolo II, 132, 84084 Fisciano, SA, Italy; European Laboratory for the Investigation of Food-Induced Diseases (ELFID), University Federico II, via Pansini 5, 80131 Naples, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Marabotti
authors.affiliation: Dept. of Biology, University Federico II, via Mezzocannone 8, 80134 Naples, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Gay
authors.affiliation: Dept. of Biology, University Federico II, via Mezzocannone 8, 80134 Naples, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Capaldo
authors.affiliation: Dept. of Chemistry and Biology, University of Salerno, via Giovanni Paolo II, 132, 84084 Fisciano, SA, Italy; European Laboratory for the Investigation of Food-Induced Diseases (ELFID), University Federico II, via Pansini 5, 80131 Naples, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Esposito
authors.affiliation: Dept. of Chemistry and Biology, University of Salerno, via Giovanni Paolo II, 132, 84084 Fisciano, SA, Italy; European Laboratory for the Investigation of Food-Induced Diseases (ELFID), University Federico II, via Pansini 5, 80131 Naples, Italy. Electronic address: icaputo@unisa.it.
authors.forename: I
authors.initials: I
authors.lastname: Caputo
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects*; D010636:Phenols / Q000633:toxicity*; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors / Q000378:metabolism; D000071717:X-Box Binding Protein 1
chemical_list: D004268:DNA-Binding Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D010636:Phenols; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; C041594:4-nonylphenol
keywords: 4-Nonylphenol; Apoptosis; Caco-2 cells; Cell proliferation; Endoplasmic-reticulum stress; Intestinal toxicity