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RESEARCH PRODUCT

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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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, A 1 , A 2 , B, B 1 , B 4 and J 3 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 IC 50 value for EN A 2 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, A 1 , B 1 and B 4 exert pronounced cytotoxic effects in all the cell lines tested by the MTT assay after 24 and 48 h of incubation. The EN A 1 demonstrated to be the most cytotoxic ENs tested. Moreover, no statistical differences were found between the IC 50 values obtained for EN A 1 on Caco-2, HT-29 and Hep-G2, with IC 50 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, B 1 and B 4 showed lower cytotoxicity, but in a similar range as the IC 50 values reported on HT-29 (IC 50 values (24 h): 16.8 ± 4.3–26.2 ± 6.7 μM), Caco-2 (IC 50 values (24 h): 19.5 ± 4.1 μM) and Hep-G2 (IC 50 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 (IC 50 values ranged from 8.2 ± 1.8 to 11.4 ± 4.6 μM), B 1 (IC 50 values variables from 3.7 ± 0.7 to 11.5 ± 5.3 μM) and B 4 (IC 50 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.