Comparative cytotoxicity study of enniatins A, A1, A2, B, B1, B4 and J3 on Caco-2 cells, Hep-G2 and HT-29 |
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Authors: | G. Meca G. FontM.J. Ruiz |
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Affiliation: | Laboratory of Food Chemistry and Toxicology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés s/n, 46100 Burjassot, Spain |
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Abstract: | Enniatins (ENs) are ionophoric, phytotoxic, antihelminthic, and antibiotic compounds of hexadepsipeptidic structure produced by several strains of Fusarium spp. The cytotoxicity effect of the ENs A, A1, A2, B, B1, B4 and J3 was compared on three tumor cell lines, the human epithelial colorectal adenocarcinoma (Caco-2), the human colon carcinoma (HT-29), and the human liver carcinoma (Hep-G2). The endpoint evaluated was the mitochondrial integrity by using the MTT assays, after 24 and 48 h of incubation. The IC50 value for EN A2 on Caco-2 cells, after 24 h exposure, was 18.7 ± 4.5 μM and decrease to 2.6 ± 0.7 μM at 48 h of incubation. However, ENs A, A1, B1 and B4 exert pronounced cytotoxic effects in all the cell lines tested by the MTT assay after 24 and 48 h of incubation. The EN A1 demonstrated to be the most cytotoxic ENs tested. Moreover, no statistical differences were found between the IC50 values obtained for EN A1 on Caco-2, HT-29 and Hep-G2, with IC50 values ranging from 9.1 ± 2.2 μM to 12.3 ± 4.3 μM at 24 h and decreasing in a range variable from 1.4 ± 0.7 μM to 2.7 ± 0.8 μM at 48 h. On the other hand, EN A, B1 and B4 showed lower cytotoxicity, but in a similar range as the IC50 values reported on HT-29 (IC50 values (24 h): 16.8 ± 4.3-26.2 ± 6.7 μM), Caco-2 (IC50 values (24 h): 19.5 ± 4.1 μM) and Hep-G2 (IC50 values (24 h): 23.4 ± 5.6-26.2 ± 7.6 μM) cells. Cytotoxic effect with a 48 h of incubation revealed also a significant toxicity of ENs A (IC50 values ranged from 8.2 ± 1.8 to 11.4 ± 4.6 μM), B1 (IC50 values variables from 3.7 ± 0.7 to 11.5 ± 5.3 μM) and B4 (IC50 of 4.5 ± 2.9-15.0 ± 4.0 μM). In summary, this study demonstrated that ENs can exert toxic activity at low micromolar concentrations in mammalian cells. |
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Keywords: | Enniatins Cytotoxicity Caco-2 Hep-G2 HT-29 |
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