title: Beauvericin-induced cytotoxicity via ROS production and mitochondrial damage in Caco-2 cells.
abstract: 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 μM. 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 (ΔΨm; 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 ΔΨm determined, were in a dose- time-dependent manner. Moreover, DNA damage was observed after 12.0 μM concentration. This study demonstrated that oxidative stress is one of the mechanism involved in BEA toxicity, moreover apoptosis induction and loss of ΔΨm contribute to its cytotoxicity in Caco-2 cells.
authors.affiliation: Laboratory of Food Chemistry and Toxicology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andres Estelles s/n, 46100 Burjassot, Valencia, Spain. Electronic address: alessandra.prosperini@uv.es.
authors.forename: A
authors.initials: A
authors.lastname: Prosperini
authors.forename: A
authors.initials: A
authors.lastname: Juan-García
authors.forename: G
authors.initials: G
authors.lastname: Font
authors.forename: M J
authors.initials: MJ
authors.lastname: Ruiz
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D047630:Depsipeptides / Q000633:toxicity*; D016195:G2 Phase / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007476:Ionophores / Q000633:toxicity*; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects*; D009183:Mycotoxins / Q000633:toxicity*; D009336:Necrosis; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D047630:Depsipeptides; D007476:Ionophores; D009183:Mycotoxins; D017382:Reactive Oxygen Species; C004456:beauvericin; D005978:Glutathione
keywords: Apoptosis; Beauvericin; Cell cycle; DNA damage; Mitochondrial membrane potential; Oxidative stress