Beauvericin is a cyclic hexadecanopeptide mycotoxin and a potent inhibitor of acyl-CoA:cholesterol acyltransferase 1 (ACAT1), which is involved in multiple tumor-related pathways[1]. Beauvericin has potential antifungal activity and is a potent inhibitor of CYP3A1/2 enzymes in human and rat liver microsomes[2]. Beauvericin also has significant inhibitory effects on CYP3A4/5 and CYP2C19, with IC50 values of 1.2μM and 1.3μM, respectively[2]. Beauvericin is active against Gram-positive bacteria and mycobacteria, and can also induce programmed cell death in mammals[3].
In vitro, treatment of CHO-K1 cells with Beauvericin (0.625-20µM) for 24-72h reduced cell viability in a dose- and time-dependent manner, altered the mitochondrial membrane potential in the cells, arrested the G0/G1 phase of the cell cycle and produced apoptosis, and increased catalase and superoxide dismutase activities[4]. Beauvericin (3.125-25µM) treated human colon adenocarcinoma Caco-2 cells for 24-72h reduced cell viability in a dose- and time-dependent manner, increased apoptosis and mitochondrial damage, and DNA damage was observed after 12μM[5]. Beauvericin (0-10µM) treated immature dendritic cells, mature dendritic cells and macrophages with IC50 values of 1.0μM, 2.9μM and 2.5μM, respectively [6].
In vivo, Beauvericin (4mg/kg) was used to treat colitis mice by intraperitoneal injection, which inhibited the pathological changes of colitis, suppressed T cell infiltration into colon tissue, and significantly reduced the levels of cytokines IFN-γ, TNF-α, IL-1β and IL-12[7].
References:
[1] Zhou H, Zhang J, Chen X, et al. Potent Anticancer Activities of Beauvericin Against KB Cells In Vitro by Inhibiting the Expression of ACAT1 and Exploring Binding Affinity[J]. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents), 2022, 22(5): 897-904.
[2] Mei L, Zhang L, Dai R. An inhibition study of beauvericin on human and rat cytochrome P450 enzymes and its pharmacokinetics in rats[J]. Journal of enzyme inhibition and medicinal chemistry, 2009, 24(3): 753-762.
[3] Olleik H, Nicoletti C, Lafond M, et al. Comparative structure–activity analysis of the antimicrobial activity, cytotoxicity, and mechanism of action of the fungal cyclohexadepsipeptides enniatins and beauvericin[J]. Toxins, 2019, 11(9): 514.
[4] Mallebrera B, Juan-Garcia A, Font G, et al. Mechanisms of beauvericin toxicity and antioxidant cellular defense[J]. Toxicology Letters, 2016, 246: 28-34.
[5] Prosperini A, Juan-García A, Font G, et al. Beauvericin-induced cytotoxicity via ROS production and mitochondrial damage in Caco-2 cells[J]. Toxicology letters, 2013, 222(2): 204-211.
[6] Ficheux A S, Sibiril Y, Parent-Massin D. Effects of beauvericin, enniatin b and moniliformin on human dendritic cells and macrophages: An in vitro study[J]. Toxicon, 2013, 71: 1-10.
[7] Wu X F, Xu R, Ouyang Z J, et al. Beauvericin ameliorates experimental colitis by inhibiting activated T cells via downregulation of the PI3K/Akt signaling pathway[J]. PloS one, 2013, 8(12): e83013.
白僵菌素（Beauvericin）是一种环状十六缩酚肽霉菌毒素，是酰基辅酶 A：胆固醇酰基转移酶 1（ACAT1）的有效抑制剂，参与多种肿瘤相关途径[1]。Beauvericin有潜在的抗真菌活性，并且是人和大鼠肝微粒体中CYP3A1/2酶的有效抑制剂[2]。Beauvericin对CYP3A4/5和CYP2C19也有显著的抑制作用，IC50值分别为1.2μM和1.3μM[2]。Beauvericin对革兰氏阳性菌和分枝杆菌具有活性，并且还能够诱导哺乳动物的程序性细胞死亡[3]。
在体外，Beauvericin（0.625-20µM）处理CHO-K1细胞24-72h，以剂量和时间依赖性方式降低细胞活力，改变了细胞中的线粒体膜电位，使细胞周期的G0 /G1期停滞并产生细胞凋亡，增加了过氧化氢酶和超氧化物歧化酶活性[4]。Beauvericin（3.125-25µM）处理人结肠腺癌Caco-2细胞24-72h，以剂量和时间依赖性方式降低细胞活力，增加了细胞凋亡和线粒体破坏，12μM后观察到 DNA损伤[5]。Beauvericin（0-10µM）处理未成熟树突状细胞、成熟树突状细胞和巨噬细胞，IC50分别为1.0μM、2.9μM和2.5μM [6]。
在体内，Beauvericin（4mg/kg）通过腹腔注射治疗结肠炎小鼠，抑制了结肠炎的病理变化，抑制了T细胞浸润到结肠组织，显著降低了细胞因子IFN-γ、TNF-α、IL-1β和IL-12的水平[7]。