Sequential events of apoptosis induced by zearalenone in cultured hepatocarcinoma cells |
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Authors: | Amel Chatti Gazzah Emna El Golli Bennour Chayma Bouaziz Salwa Abid Moncef Ladjimi Hassen Bacha |
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Institution: | (1) Laboratory of Research on Biologically Compatible Compounds, Faculty of Dentistry, Rue Avicenne, Monastir, 5000, Tunisia;(2) Laboratory of Genetic and Cellular Biology, CNRS, UMR 8159, Versailles St-Quentin University, 45 Avenue des Etats-Unies, Versailles, 78035, France; |
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Abstract: | Zearalenone (ZEA) is a fungal metabolite that can contaminate feed and foodstuffs and can cause serious health problems for
animals as well as for humans. The present investigation was conducted to determine the chronological succession of the main
events that characterise ZEA-induced toxicity in human hepatocarcinoma cells. To this aim, we have monitored the effects of
ZEA on (1) cell viability, (2) heat-shock protein expression, (3) oxidative damage, (4) DNA fragmentation, (5) the cell cycle
and (6) the cell-death-signalling pathway. Our results demonstrated that ZEA reduced cell viability in a time- and dose-dependent
manner. When we exposed HepG2 cells to 100 μM ZEA (80% of cells are viable) for different treatment times (2, 4, 8, 24, 30, 48 and 60 h), we demonstrated an induction
of Hsp70 protein, an increase in reactive oxygen species (ROS) generation, DNA fragmentation and cell-cycle arrest. These
events begin after only 2 h of mycotoxin exposure and are earlier than those implicated in the execution of apoptosis. However,
significant apoptotic cell death was observed after at least 30 h of ZEA exposure as a consequence of increased Bax expression,
decreased Bcl-2 expression and mitochondrial membrane potential (Δψm)-released cytochrome c and activated caspase-3 and caspase-9. |
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