title: Mechanism of Alternariol monomethyl ether-induced mitochondrial apoptosis in human colon carcinoma cells.
abstract: Alternariol monomethyl ether (AME) is a major mycotoxin produced by fungi of the genus Alternaria and a common contaminant of food products such as fruits and cereals worldwide. AME can cause serious health problems for animals as well as for humans. In this study, human colon carcinoma cells (HCT116) were used to explore the mechanisms of cell death induced by AME. Exposure of HCT116 cells to AME resulted in significant cytotoxicity manifested by a loss in cell viability mainly mediated by activation of apoptotic process. AME activated the mitochondrial apoptotic pathway evidenced by the opening of the mitochondrial permeability transition pore (PTP), loss of the mitochondrial transmembrane potential (ΔΨm) downstream generation of O(2)(-), cytochrome c release and caspase 9 and 3 activation. Experiments conducted on isolated organelles indicated that AME does not directly target mitochondria to induce PTP-dependent permeabilization of mitochondrial membranes. Moreover, no difference was observed in Bax-KO cells in comparison to parental cells, suggesting that the pro-apoptotic protein Bax is not involved in AME-induced mitochondrial apoptosis. Our findings demonstrate for the first time that AME induces cell death in human colon carcinoma cells by activating the mitochondrial pathway of apoptosis.
authors: Laboratory for Research on Biologically Compatible Compounds, Faculty of Dentistry, Rue Avicenne, 5019 Monastir, Tunisia.
authors: Fatma
authors: F
authors: Bensassi
authors: Cindy
authors: C
authors: Gallerne
authors: Ossama Sharaf
authors: OS
authors: el Dein
authors: Mohamed Rabeh
authors: MR
authors: Hajlaoui
authors: Hassen
authors: H
authors: Bacha
authors: Christophe
authors: C
authors: Lemaire
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007783:Lactones / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism; D009183:Mycotoxins / Q000494:pharmacology*; D010539:Permeability; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D007783:Lactones; D009183:Mycotoxins; D051028:bcl-2-Associated X Protein; C018206:alternariol monomethyl ether