Beauvericin and enniatin: emerging toxins and/or remedies?

Abstract

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-κB 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.