title: Involvement of mitochondria-mediated apoptosis in deoxynivalenol cytotoxicity.
abstract: Deoxynivalenol (DON) is a widespread trichothecene mycotoxin which contaminates cereal crops and harmfully affects the gastrointestinal tract. Since it is well known that mitochondria play a central role in apoptosis triggered by many stimuli, an effort was made to examine whether DON-induced cytotoxicity occurs through mitochondria-mediated apoptotic pathway. The intestinal system being one of the primary targets of mycotoxins, the human colon carcinoma cell line HCT116 was used in this study. Using flow cytometric analyses and immunofluorescence, we showed that DON at 100 μM induced a mitochondria-dependent apoptotic pathway associated with opening of the mitochondrial permeability transition pore (PTP), loss of the mitochondrial transmembrane potential (ΔΨm), downstream generation of O₂·⁻ and cytochrome c release. The DON-induced apoptosis was accompanied by an activation of caspase 9 and 3, as demonstrated by Western blot and caspase activity assay. In addition, by taking advantage of HCT116 cells invalidated for Bax, we showed that this pro-apoptotic protein favored mitochondrial alterations induced by the mycotoxin. Besides, incubation of purified mitochondria with DON indicated that this mycotoxin does not directly target mitochondria to induce PTP-dependent permeabilization of mitochondrial membranes. Altogether, our results indicate that mitochondria-related caspase-dependent apoptotic pathway is involved in this in vitro model of DON induced-cytotoxicity.
authors.affiliation: Laboratory for Research on Biologically Compatible Compounds, Faculty of Dentistry, Rue Avicenne, 5019 Monastir, Tunisia.
authors.forename: Fatma
authors.initials: F
authors.lastname: Bensassi
authors.forename: Cindy
authors.initials: C
authors.lastname: Gallerne
authors.forename: Ossama
authors.initials: O
authors.lastname: Sharaf El Dein
authors.forename: Christophe
authors.initials: C
authors.lastname: Lemaire
authors.forename: Mohamed Rabeh
authors.initials: MR
authors.lastname: Hajlaoui
authors.forename: Hassen
authors.initials: H
authors.lastname: Bacha
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects*; D014255:Trichothecenes / Q000633:toxicity*
chemical_list: D014255:Trichothecenes; D045304:Cytochromes c; D020169:Caspases; D020782:Matrix Metalloproteinases; C007262:deoxynivalenol