Beauvericin-induced cytotoxicity via ROS production and mitochondrial damage in Caco-2 cells

The cytotoxicity of beauvericin (BEA) on human colon adenocarcinoma (Caco-2) cells was studied as a function of time. Moreover, the oxidative damage and cell death endpoints were monitored after 24, 48 and 72 h. After BEA exposure, the IC50 values ranged from 1.9 +/- 0.7 to 20.6 +/- 6.9 mu M. A decrease in reduced glutathione (GSH; 31%) levels, as well as an increase in oxidized glutathione (GSSG, 20%) was observed. In the presence of BEA, reactive oxygen species (ROS) level was highly increased at an early stage with the highest production of 2.0-fold higher than the control that was observed at 120 min. BEA induced cell death by mitochondria-dependent apoptotic process with loss of the mitochondrial membrane potential (Delta Psi m; 9% compared to the control), increase in LPO level (from 120% to 207% compared to the control) and reduced G0/G1 phase, with an arrest in G2/M, in a dose and time-dependent manner. Cell proliferation, apoptosis and Delta Psi m determined, were in a dose-time-dependent manner. Moreover, DNA damage was observed after 12.0 mu M concentration. This study demonstrated that oxidative stress is one of the mechanism involved in BEA toxicity, moreover apoptosis induction and loss of Delta Psi m contribute to its cytotoxicity in Caco-2 cells. (C) 2013 Elsevier Ireland Ltd. All rights reserved.