title: Oxidative stress and DNA interactions are not involved in Enniatin- and Beauvericin-mediated apoptosis induction.
abstract: The fusariotoxins beauvericin (BEA) and the structurally related enniatins (ENN) are frequent contaminants of grain-based food and feed. They exert potent cytotoxic activities based on apoptosis induction. Since it is known, that reactive oxygen species (ROS) and DNA damage lead to apoptotic cell death, this study aimed to clarify whether oxidative stress and DNA interactions are involved in ENN- and BEA-induced cytotoxicity. Diverse cellular and molecular assays indicated that oxidative stress does not contribute to ENN- and BEA-induced cytotoxicity. In contrast, both fusariotoxins were shown to exert moderate antioxidative activities. Moreover, only at high concentrations (>100 microM) both mycotoxins were found to intercalate substantially into dsDNA and to inhibit the catalytic activity of topoisomerase I and II. Furthermore, the potent cytotoxic activity of ENN and BEA was shown to be widely independent of cellular mismatch- and nucleotide excision repair pathways. Also the ataxia-telangiectasia mutated (ATM) protein kinase, a well known DNA damage sensor, did not affect BEAs cytotoxic potential while in ENN-induced cytotoxicity ATM had a detectable but not a major modulating influence. Together, our data suggest that ROS and DNA damage are not key factors in ENN- and BEA-mediated cytotoxicity.
authors: Department of Medicine I, Institute of Cancer Research, Medical University of Vienna, Vienna, Austria.
authors: Rita
authors: R
authors: Dornetshuber
authors: Petra
authors: P
authors: Heffeter
authors: Rosa
authors: R
authors: Lemmens-Gruber
authors: Leonilla
authors: L
authors: Elbling
authors: Doris
authors: D
authors: Marko
authors: Michael
authors: M
authors: Micksche
authors: Walter
authors: W
authors: Berger
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004249:DNA Damage; D004260:DNA Repair; D047630:Depsipeptides / Q000494:pharmacology*; D006801:Humans; D018384:Oxidative Stress; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors
chemical_list: D000975:Antioxidants; D047630:Depsipeptides; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; C100264:enniatins; C004456:beauvericin