Comparative cytotoxicity study of enniatins A, A₁, A₂, B, B₁, B₄ and J₃ on Caco-2 cells, Hep-G₂ and HT-29

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 24h 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 24h 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 (24h): 16.8 ± 4.3-26.2 ± 6.7 μM), Caco-2 (IC(50) values (24h): 19.5 ± 4.1 μM) and Hep-G2 (IC(50) values (24h): 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.