Cell death induced by the Alternaria mycotoxin Alternariol.

Abstract

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 O(2)(*-) 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.

• Authors: Fatma Bensassi, Cindy Gallerne, Ossama Sharaf El Dein, Mohamed Rabeh Hajlaoui, Hassen Bacha, Christophe Lemaire
• Journal: Toxicology in vitro : an international journal published in association with BIBRA (Toxicol In Vitro) Vol. 26 Issue 6 Pg. 915-23 (Sep 2012) ISSN: 1879-3177 [Electronic] England
• PMID: 22542754 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• BAX protein, human
• Lactones
• Mycotoxins
• Reactive Oxygen Species
• Tumor Suppressor Protein p53
• bcl-2-Associated X Protein
• Caspase 3
• alternariol

Topics

• Alternaria
• Caspase 3 (metabolism)
• Cell Death (drug effects)
• Cell Survival (drug effects)
• DNA Fragmentation
• HCT116 Cells
• Humans
• Lactones (toxicity)
• Membrane Potential, Mitochondrial (drug effects)
• Mycotoxins (toxicity)
• Reactive Oxygen Species (metabolism)
• Tumor Suppressor Protein p53 (metabolism)
• bcl-2-Associated X Protein (metabolism)