Enniatin B

Enniatin B is a Fusarium mycotoxin that acts as an ionophore to form cation-selective membrane channels, disrupt ion homeostasis and mitochondrial function, inhibit cell proliferation, and induce apoptosis, while modulating ERK, p38 MAPK, and STAT3 signaling pathways. Enniatin B is used in research on atherosclerosis, hypercholesterolemia, cervical cancer, and colon adenocarcinoma^{[1][2][3][4][5][6][7][8][9][10][11]}. In Vitro:Enniatin B (EnnB) (1.5-100 μM; 24 h) effectively reduces cellular ATP levels in Balb 3T3 and HepG2 cells in cell viability assays without disrupting plasma membrane integrity, with ED₅₀ values of 8.4 μM and 2.9 μM, respectively^[1].
Enniatin B (3-12 μM; 24 h) effectively inhibits the proliferation of Balb 3T3 and HepG2 cells in cell proliferation assays, with ED₅₀ values of 4.24 μM and 0.50 μM, respectively^[1].
Enniatin B (11-45 μM; 24-48 h) induces a slight dose-dependent increase in early apoptotic Balb 3T3 cells, with the majority of cells remaining intact^[1].
Enniatin B (0.00156-15.6 μM; 48 h) shows no specific agonistic or antagonistic effects on the transcriptional activity of estrogen, androgen, progesterone, or glucocorticoid receptors in reporter gene assays after 48 h^[3].
Enniatin B (0.1-10 μM; 48 h) reduces the viability of CCF-STTG1 human astrocytoma cells with an IC₅₀ of 8.9 μM; at concentrations above 5 μM, it moderately reduces the viability of primary porcine brain capillary endothelial cells; and after 48 h of treatment, it has no effect on the viability of HBMEC human brain microvascular endothelial cells at concentrations up to 10 μM^[10].
Enniatin B (0.1-2.5 μM; 48 h) induces a 2.7-fold increase in caspase-3 activity in CCF-STTG1 human astrocytoma cells after 48 h of treatment at a concentration of 2.5 μM, indicating activation of the apoptotic signaling pathway^[10].
Enniatin B (10 μM; 4 h) induces widespread downregulation of genes related to metabolism and mitochondrial structure in rat primary hepatocytes, including complex I subunits Ndufs1, Ndufs4, and Ndufs8, which is consistent with the manifestations of mitochondrial dysfunction and energy depletion^[1].
Enniatin B exhibits cytotoxic effects on human HepG2 cells, with potency varying widely depending on the assay method (ED₅₀ of 0.50 μM by BrdU ELISA and IC₅₀ greater than 435.9 μM by Alamar Blue)^[2].
Enniatin B (3 h) induces ROS production in human Caco-2 cells through a mitochondria-mediated cytotoxic pathway^[2].
Enniatin B (48 h) induces G₀/G₁ phase cell cycle arrest in human HepG2 cells^[2].
Enniatin B (1.25-10 μM; 24 h) induces G0/G1 phase cell cycle arrest in mouse RAW 264.7 macrophages^[2].
Enniatin B (3 μM; 72 h) induces G2/M phase cell cycle arrest in human Caco-2 cells, accompanied by a decrease in S phase cells and accumulation of cells in the SubG0/G1 phase^[2].
Enniatin B (48 h) induces apoptosis and necrotic cell death in human Caco-2 cells^[2].
Enniatin B (1.5-3.0 μM; 48 h) induces apoptosis in human HepG2 cells without causing necrosis^[2].
Enniatin B (0.66 μM; 2.5-30 min) undergoes extensive phase I metabolism via oxidation and N-demethylation in rat, dog, and human liver microsomes, producing 12 identified metabolites, with species-dependent metabolic profiles, and the intrinsic clearance in dog liver microsomes is approximately 7-fold higher than that in rat and human liver microsomes^[7].
Enniatin B (0.1-20 μM; 4 h) shows no mutagenicity up to cytotoxic concentrations of 20 μM in the HPRT assay in V79 cells in the presence and absence of rat liver S9 metabolic activation^[8].
Enniatin B (0.1-100 μM; 3-18 h) does not induce significant DNA strand breaks or oxidative DNA base damage in V79 cells, as determined by standard and FPG-modified alkaline comet assays^[8].
Enniatin B (up to 10 μM; 18 h) does not induce micronuclei in V79 cells, indicating a lack of clastogenic and aneugenic activity^[8].
Enniatin B (1 μM; 24 h) induces nuclear fragmentation, a marker of apoptosis, in approximately 10% of V79 cells^[8].
Enniatin B (0.1-2.5 μM; 48 h) does not induce significant LDH leakage in CCF-STTG1 human astrocytoma cells at concentrations up to 2.5 μM after 48 h of treatment, suggesting that necrosis is not the primary mode of cell death^[10].
Enniatin B (0.01-100 μM; 48 h) reduces the viability of H295R cells in a dose-dependent manner, with viability decreasing by 37% after 48 h of treatment at 100 μM^[3].
Enniatin B (0.01-100 μM; 48 h) reduces the viability of unstimulated and LH-stimulated neonatal porcine Leydig cells by approximately 20%^[3].
Enniatin B (0.00156-15.6 μM; 48 h) reduces the viability of TARM-Luc, TM-Luc, and TGRM-Luc reporter gene cell lines after 48 h treatment at 15.6 μM, with minimal effect on MMV-Luc cells^[3].
Enniatin B (30 min pre-incubation with inhibitors), when combined with MEK1/2 or p38 MAPK inhibitors, induces enhanced cytotoxicity in KB-3-1 cervical cancer cells, suggesting that both ERK and p38 pathways promote cell survival under Enniatin B treatment^[11].
Enniatin B (2-3 μM; 48 h), when combined with pharmacological p38 MAPK inhibition, induces decreased Hsp27 phosphorylation levels in KB-3-1 cervical cancer cells^[11].
Enniatin B (0.1-25 μM; 24-72 h) induces S phase arrest, a decreased G₀/G₁ phase proportion, and apoptosis in H295R cells in a time- and dose-dependent manner, with an apoptosis rate of 32.2% after 72 h of treatment at 25 μM^[3].
Enniatin B (0.01-100 μM; 48 h) decreases progesterone, testosterone, and cortisol production in H295R cells, while estradiol levels remain unchanged^[3].
Enniatin B (10 μM; 48 h) modulates the expression of 12 out of 16 steroidogenesis-related genes in H295R cells after 48 h of treatment, with downregulation of early pathway genes (HMGR, StAR, CYP11A, HSD3B2, CYP17A1) and upregulation of other steroidogenic and biotransformation genes^[3].
Enniatin B (0.01-100 μM; 48 h) reduces estradiol and testosterone production in LH-stimulated neonatal porcine Leydig cells, with minimal effects on unstimulated cells^[3].
Enniatin B (56 pM-437.2 μM; 3-24 h) effectively impairs lysosomal function in Caco-2 cells in a time- and concentration-dependent manner, with a 24 h EC₅₀ of 2.1 μM, without affecting metabolic activity or membrane integrity at the tested concentrations^[5].
Enniatin B (1-50 μM; 3-24 h) induces rapid and concentration-dependent lysosomal membrane permeabilization in Caco-2 cells, with damage detectable as early as 3 h and pronounced disruption at 24 h^[5].
Enniatin B (1-25 μM; 24 h) decreases Caco-2 cell proliferation in a concentration-dependent manner, with a 50% reduction in proliferation at 25 μM after 24 h, accompanied by progressive morphological changes and cell detachment^[5].
Enniatin B (1-25 μM; 24 h) causes a slight but detectable G₂/M phase cell cycle arrest in Caco-2 cells after 24 h treatment at 25 μM, without leading to significant accumulation of sub-G₁ phase cells^[5].
Enniatin B (24 h) as a single agent has only a minimal effect on DNA synthesis in KB-3-1 cervical cancer cells^[11].
Enniatin B (24-48 h) induces moderate G₀/G₁ phase cell cycle arrest in KB-3-1 cervical cancer cells, and this effect is more pronounced after 48 h of treatment^[11].
Enniatin B (1-25 μM; 24 h) predominantly induces necrotic cell death in Caco-2 cells in a dose-dependent manner, with necrotic cells accounting for approximately 13% after 24 h treatment at 25 μM, and with minimal apoptosis^[5].
Enniatin B (5-10 μM; 3-24 h) induces dose-dependent changes in mitochondrial membrane permeability in Caco-2 cells, an effect detectable as early as 3 h and more pronounced at 24 h, which is not mediated by cathepsins^[5].
Enniatin B (1-25 μM; 3-24 h) induces a 2.4-fold increase in intracellular ROS levels in Caco-2 cells after 24 h treatment at 5 μM, an effect that is completely inhibited by the antioxidant ascorbic acid^[5].
Enniatin B (1-10 μM; 24 h) induces the release of cathepsins B and D from lysosomes into the cytosol of Caco-2 cells in a concentration-dependent manner after 24 h of exposure, with altered processing, which is consistent with lysosomal membrane permeabilization^[5].
Enniatin B (5 μM; 24 h) treatment leads to the appearance of mature caspases (caspase-14, -6, -3) and the pro-apoptotic proteins Bax and Bid in the cytoplasm of Caco-2 cells, which is consistent with the activation of cell death pathways^[5].
Enniatin B (0.009-100 μM; 24-72 h) exerts potent multiparametric hepatotoxic effects in Hep-G2 cells, with significant toxicity observed at 0.9 μM after 24 h and 72 h of exposure^[6].
Enniatin B (100 nM-100 μM; 20 min preincubation, 2-day culture) is not mutagenic to Salmonella typhimurium strains TA 98, TA 100, TA 102, and TA 104 in the presence or absence of rat liver S9 metabolic activation, with the highest tested toxic concentration being 100 μM^[8].
Enniatin B (4-10 μM; 24 h) exhibits potent cytotoxicity against human umbilical cord blood-derived immature dendritic cells, mature dendritic cells, and macrophages, with IC₅₀ values of 1.6 μM, 2.6 μM, and 2.5 μM, respectively^[9].
Enniatin B (1-1.3 μM; 5 days) does not alter CD1a expression during the differentiation of human umbilical cord blood monocytes into immature dendritic cells at concentrations of 1 μM and 1.3 μM^[9].
Enniatin B (1-1.3 μM; 5 days) does not affect the endocytic capacity during the differentiation of human umbilical cord blood monocytes into immature dendritic cells at concentrations of 1 μM and 1.3 μM^[9].
Enniatin B (0.5-1 μM; 6 days) reduces the endocytic capacity during the differentiation of human umbilical cord blood monocytes into macrophages^[9].
Enniatin B (0.5-1 μM; 6 days) does not alter respiratory burst activity during the differentiation of human umbilical cord blood monocytes into macrophages at concentrations of 0.5 μM and 1 μM^[9].
Enniatin B (0.5-1 μM; 6 days) upregulates CD71 expression in a dose-dependent manner during the differentiation of human umbilical cord blood monocytes into macrophages, while the expression of CD11a, HLA-DR, CD80, and CD54 remains unchanged^[9].
Enniatin B (1-2 μM; 2 days) downregulates the maturation markers CD80, CD86, and CCR7 during Lipopolysaccharides, from E. coli O55:B5 (HY-D1056)-induced maturation of human cord blood-derived dendritic cells at 2 μM, while HLA-DR expression remains unaffected^[9].
Enniatin B (1-2 μM; 2 days) increases IL-10 secretion during LPS-induced maturation of human umbilical cord blood-derived dendritic cells^[9].
Enniatin B (0.5-1 μM; 6 days) does not alter TNF-α secretion during the differentiation of human umbilical cord blood monocytes into macrophages at concentrations of 0.5 μM and 1 μM^[9].
Enniatin B (72 h) inhibits the viability of multiple human cancer cell lines with low micromolar potency, with IC₅₀ values ranging from 1.74 μM (HTB-31 cervical cancer) to > 10 μM (Caki-2 renal cell carcinoma)^[11].
Enniatin B (3 μM; 24 h) induces mitochondrial membrane depolarization and increases the proportion of late apoptosis/necrosis in KB-3-1 cervical cancer cells after 24 h of treatment^[11].
Enniatin B (1-3 μM; 48 h) modulates the expression of apoptosis-related proteins in KB-3-1 cervical cancer cells, inducing caspase-7 activation, PARP cleavage, upregulation of the pro-apoptotic genes bak and bim, and downregulation of the pro-survival genes bcl-xL and Mcl-1^[11].
Enniatin B (1-3 μM; 48 h) modulates the expression of cell cycle proteins in KB-3-1 cervical cancer cells, and its mode of action is consistent with G₀/G₁ phase cell cycle arrest^[11].
Enniatin B (1-3 μM; 48 h) modulates multiple MAPK signaling pathways in KB-3-1 cervical cancer cells, inhibiting ERK phosphorylation while strongly activating p38 MAPK and its downstream target CREB, and reducing STAT3 phosphorylation levels^[11].
Enniatin B (2.5 μM; 20 h) effectively inhibits capillary-like tube formation in human umbilical vein endothelial cells at subtoxic concentrations^[11].
Enniatin B (4 μM; 15 h) strongly inhibits VEGF-induced migration of human umbilical vein endothelial cells^[11]. In Vivo:Enniatin B (5 mg/kg; i.p.; once daily; for 2 consecutive days) does not cause acute tissue damage in mice, but accumulates in lipophilic tissues^[2].
Enniatin B (1.25-40 mg/kg; i.p.; every 8 h) causes death in mice within 2 to 5 days at doses of 10 mg/kg and above, reduces body weight, and shows no anti-HIV activity in mice^[2].
Enniatin B (0.2 mg/kg; intravenous bolus; single dose) is widely distributed in broiler tissues, with an average volume of distribution of 33.91 L/kg^[2].
Enniatin B (0.05 mg/kg; oral bolus; single dose) exhibits a higher absorption extent than ENN B1, ENN A1, and ENN A in pigs^[2].
Enniatin B (1.03 mg/kg; p.o.), as a component of a mixture of four enniatins, produces no adverse effects in Wistar rats^[2].
Enniatin B (5 mg/kg; i.p.; once daily; for 2 consecutive days) is well tolerated in healthy SCID mice, accumulates mainly in the liver and fat, and is extensively metabolized into three phase I metabolites in the liver and intestine^[4].
Enniatin B (5 mg/kg; i.p.; once daily; for 9 consecutive days) is well tolerated in mice bearing KB-3-1 cervical cancer xenografts and accumulates in tumor tissue at a concentration of 2.8 μg/kg^[4].
Enniatin B (5 mg/kg; i.p.; once daily; for 14 days) as a single agent does not significantly reduce the growth of KB-3-1 cervical cancer xenografts in SCID mice^[11].