Cell death induced by the Alternaria mycotoxin Alternariol

• Published in: Toxicology in vitro 2012-09, Vol.26 (6), p.915-923
• Main Authors: Bensassi, Fatma, Gallerne, Cindy, Sharaf El Dein, Ossama, Hajlaoui, Mohamed Rabeh, Bacha, Hassen, Lemaire, Christophe
• Format: Article
• Language: English
• Subjects: Alternaria; Alternariol; Apoptosis; bcl-2-Associated X Protein - metabolism; Caspase; Caspase 3 - metabolism; Cell Death - drug effects; Cell Survival - drug effects; DNA Fragmentation; HCT116 Cells; Humans; Lactones - toxicity; Membrane Potential, Mitochondrial - drug effects; Mitochondria; Mycotoxins - toxicity; PTP; Reactive Oxygen Species - metabolism; Tumor Suppressor Protein p53 - metabolism; ΔΨm
• ISSN: 0887-2333; 1879-3177
• DOI: 10.1016/j.tiv.2012.04.014

► AOH induced a mitochondrial apoptotic pathway. ► AOH triggered the opening of the mitochondrial permeability transition pore (PTP). ► AOH induced a loss of the mitochondrial transmembrane potential (ΔΨm). ► AOH does not directly target mitochondria. ► Bax is partially involved in AOH-induced mitochondrial apoptosis. Mycotoxins are unavoidable contaminants of most foods and feeds, and some are known to be detrimental to human health. It is thus worthwhile to understand how cells of the intestinal system, one of the primary targets of these toxins, respond to their toxic effects. In this study, human colon carcinoma cells were used to elucidate the cell death mode and the pathways triggered by Alternariol (AOH), the most important mycotoxin produced by Alternaria species, which are the most common mycoflora infecting small grain cereals worldwide. Treatment of cells with AOH resulted in a loss of cell viability by inducing apoptosis. AOH-induced apoptosis was mediated through a mitochondria-dependent pathway, characterized by a p53 activation, an opening of the mitochondrial permeability transition pore (PTP), a loss of mitochondrial transmembrane potential (ΔΨm), a downstream generation of O2- and caspase 9 and 3 activation. Besides, deficiency of the pro-apoptotic protein Bax partially protected cells against AOH-induced mitochondrial alterations. In addition, experiments performed on purified mitochondria indicated that AOH does not directly target this organelle to induce cell death. Our results demonstrate for the first time that AOH-induced cytotoxicity is mediated by activation of the mitochondrial pathway of apoptosis in human colon carcinoma cells.