Beauvericin (BEA) and enniatins (ENN) are emerging Fusarium mycotoxins that are known to contaminate food and feed BEA- and ENN-mediated cytotoxicity towards various mammalian and cancer cell lines is only partly understood yet and engages several cellular targets and molecular mechanisms Thus, the channel forming ability of BEA and ENN selectively directs a flux of cations particularly calcium into the cell The resulting increased intracellular calcium levels might be at least in part responsible for their cytotoxicity Additionally, BEA and ENN activate programmed cell death via the internal mitochondrial pathway (release of cytochrome c, activation of pro-apoptotic proteins such as Bax and activation of caspases) Several cellular signalling pathways and regulators are influenced by these fusariotoxins including MAPK, NF-kappa B and p53 The in vitro cytotoxicity implicates that these compounds could be potentially used as cancer therapeutics However, considering their high prevalence in grains destined for consumption, also potential systemic toxicity towards humans and animals has to be considered Interestingly, the few studies that have addressed this issue in animals so far predominantly reported minor effects at least as far as acute toxicity is concerned However, consequences especially of chronic exposure but also at pharmacologically active doses in humans/animals have not been explored in detail Nevertheless, both compounds exhibit interesting pharmacological characteristics (as they are cytotoxic especially to cancer cells, inhibit drug efflux pumps, are non-mutagenic, inhibit bone resorption) which suggest them as potential drug candidates to fight disseminated cancer Thus, detailed studies on the consequences of chronic and bolus BEA and ENN exposure are eagerly needed
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Univ Ghent, Fac Vet Med, Dept Med Imaging & Small Anim Orthopaed, Salisburylaan 133, Merelbeke, BelgiumUniv Ghent, Fac Pharmaceut Sci, Dept Pharmaceut Anal, Drug Qual & Registrat DruQuaR Grp, Ottergemsesteenweg 460, B-9000 Ghent, Belgium
Peremans, Kathelijne
Burvenich, Christian
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Univ Ghent, Fac Vet Med, Dept Comparat Physiol & Biometr, Salisburylaan 133, Merelbeke, BelgiumUniv Ghent, Fac Pharmaceut Sci, Dept Pharmaceut Anal, Drug Qual & Registrat DruQuaR Grp, Ottergemsesteenweg 460, B-9000 Ghent, Belgium
Burvenich, Christian
Delesalle, Catherine
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Univ Ghent, Fac Vet Med, Dept Comparat Physiol & Biometr, Salisburylaan 133, Merelbeke, BelgiumUniv Ghent, Fac Pharmaceut Sci, Dept Pharmaceut Anal, Drug Qual & Registrat DruQuaR Grp, Ottergemsesteenweg 460, B-9000 Ghent, Belgium
Delesalle, Catherine
De Spiegeleer, Bart
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Univ Ghent, Fac Pharmaceut Sci, Dept Pharmaceut Anal, Drug Qual & Registrat DruQuaR Grp, Ottergemsesteenweg 460, B-9000 Ghent, BelgiumUniv Ghent, Fac Pharmaceut Sci, Dept Pharmaceut Anal, Drug Qual & Registrat DruQuaR Grp, Ottergemsesteenweg 460, B-9000 Ghent, Belgium
机构:
Univ Milan, Dept Vet Med, Via Univ 6, I-26900 Lodi, ItalyUniv Milan, Dept Vet Med, Via Univ 6, I-26900 Lodi, Italy
Serra, Valentina
Salvatori, Giancarlo
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Univ Molise, Dept Med & Sci Hlth V Tiberio, Via Francesco Sanctis 1, I-86100 Campobasso, ItalyUniv Milan, Dept Vet Med, Via Univ 6, I-26900 Lodi, Italy
Salvatori, Giancarlo
Pastorelli, Grazia
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Univ Milan, Dept Vet Med, Via Univ 6, I-26900 Lodi, ItalyUniv Milan, Dept Vet Med, Via Univ 6, I-26900 Lodi, Italy