Cytotoxic effects of the mycotoxin beauvericin to human cell lines of myeloid origin

Abstract

Beauvericin, a cyclic hexadepsipeptide of potential importance to the health of humans and domestic animals, has been reported to exert cytotoxic effects on several mammalian cell types and to induce apoptosis. We investigated the cytotoxicity of this compound to two human cell lines of myeloid origin: the monocytic lymphoma cells U-937 and the promyelocytic leukemia cells HL-60. In some experiments HL-60 cells partially differentiated towards the eosinophilic phenotype were also used. Cultures of U-937 cells and HL-60 cells in stationary phase were exposed to beauvericin at concentrations ranging from 100 nM to 300 μM for periods of time of 4 and 24 h, respectively. The effects of beauvericin on cell viability were assessed by the Trypan blue exclusion method. In another set of experiments, performed with U-937 cells, the mycotoxin was included in the culture medium at passaging, in order to assess its possible effects on cell growth. Viability of both U-937 cells and HL-60 cells was not affected by beauvericin at concentrations up to 3 μM, after 4 h exposure, whereas a steady decline was seen at higher concentrations. Similarly, after an exposure time of 24 h, a decline in viability was observed in cultures exposed to beauvericin at a concentration of 10 μM or higher. Thus, 50% cytotoxic concentrations at 24 h of ≅30 μM and ≅15 μM were estimated for U-937 cells and HL-60 cells, respectively. Similar experiments were performed with cultures of HL-60 cells partially differentiated towards the eosinophilic phenotype, revealing that, in 4 h exposure experiments (but not in 24 h experiments), the viability of these cultures underwent a significantly less pronounced decline, in comparison to undifferentiated HL-60 cultures. Interestingly, when U-937 cells were allowed to proliferate in the presence of the mycotoxin, included in the culture medium at passaging, a substantial cytotoxicity was observed at lower concentrations, compared with prevalently resting, stationary phase cultures. Accordingly, a definite inhibition of the proliferative capability of the cells was detected. The information provided by this work may be useful in selecting appropriate myeloid cell models for the development of biossays aimed at detecting beauvericin (and, possibly, other mycotoxins) in foods and other commodities.