Iturin A

Iturin A is a cyclic lipopeptide derived from Bacillus subtilis and related bacteria, which has strong antifungal activity against pathogenic yeast and fungi^[1]. Iturin A can interact with ergosterol in the cytoplasmic membrane, leading to the formation of ion conduction pores and the outflow of intracellular ions, such as K^+[2]. Iturin A has antiviral and antitumor activities^[3].

In vitro, Iturin A (5-100μM) treatment of HepG2 cells for 48h inhibited cell growth in a concentration-dependent manner, significantly increased the proportion of cells in the G2/M phase, reduced the proportion of cells in the S phase, induced cell apoptosis, and led to an increase in intracellular ROS^[4]. Iturin A (0-20μM) treated breast cancer MDA-MB-231 and MCF-7 cells for 48h significantly inhibited cell proliferation, with IC₅₀ values of 7.98±0.19μM and 12.16±0.24μM, respectively. It induced cell apoptosis, changed the expression profile of proteins involved in cell apoptosis, and inhibited Akt kinase activity in cells^[5]. Iturin A (0-100μM) treated Caco-2 cells for 48h inhibited cell growth in a concentration-dependent manner, induced cell apoptosis, upregulated the expression of apoptotic gene bax, and downregulated the expression of anti-apoptotic gene bcl-2^[6].

In vivo, Iturin A (5, 10, 15mg/kg) was injected into the tail vein of mice bearing sarcoma 180 cells for 28 days, which significantly inhibited tumor growth, induced tumor cell apoptosis, upregulated Bax expression, increased caspase and PARP cleavage, and downregulated the expression of CD31, Ki67, pAkt, and pMAPK^[7].

References:
[1] Yaraguppi D A, Bagewadi Z K, Patil N R, et al. Iturin: a promising cyclic lipopeptide with diverse applications[J]. Biomolecules, 2023, 13(10): 1515.
[2] Wang J, Qiu J, Yang X, et al. Identification of Lipopeptide Iturin A Produced by Bacillus amyloliquefaciens NCPSJ7 and Its Antifungal Activities against Fusarium oxysporum f. sp. niveum[J]. Foods, 2022, 11(19): 2996.
[3] Zhao H, Zhao X, Lei S, et al. Effect of cell culture models on the evaluation of anticancer activity and mechanism analysis of the potential bioactive compound, iturin A, produced by Bacillus subtilis[J]. Food & function, 2019, 10(3): 1478-1489.
[4] Zhao H, Yan L, Guo L, et al. Effects of Bacillus subtilis iturin A on HepG2 cells in vitro and vivo[J]. AMB Express, 2021, 11(1): 67.
[5] Dey G, Bharti R, Dhanarajan G, et al. Marine lipopeptide Iturin A inhibits Akt mediated GSK3β and FoxO3a signaling and triggers apoptosis in breast cancer[J]. Scientific reports, 2015, 5(1): 10316.
[6] Zhao H, Xu X, Lei S, et al. Iturin A‐like lipopeptides from Bacillus subtilis trigger apoptosis, paraptosis, and autophagy in Caco‐2 cells[J]. Journal of Cellular Physiology, 2019, 234(5): 6414-6427.
[7] Dey G, Bharti R, Banerjee I, et al. Pre-clinical risk assessment and therapeutic potential of antitumor lipopeptide ‘Iturin A’in an in vivo and in vitro model[J]. RSC advances, 2016, 6(75): 71612-71623.

Iturin A是一种源自枯草芽孢杆菌和相关细菌的环状脂肽，对致病性酵母和真菌具有较强的抗真菌（antifungal）活性^[1]。Iturin A能够与细胞质膜中的麦角甾醇相互作用，导致离子传导孔的形成和细胞内离子的流出，例如K^+[2]。Iturin A具有抗病毒、抗肿瘤活性^[3]。

在体外，Iturin A（5-100μM）处理HepG2细胞48h，以浓度依赖性的方式抑制了细胞的生长，显著增加了G2/M期细胞比例，减少了S期细胞比例，诱导了细胞凋亡，导致了细胞内ROS增加^[4]。Iturin A（0-20μM）处理乳腺癌MDA-MB-231和MCF-7细胞48h，显著抑制了细胞增殖，IC₅₀ 值分别7.98±0.19μM、12.16±0.24μM，诱导了细胞凋亡，改变了参与细胞凋亡的蛋白质的表达谱，抑制了细胞中的Akt激酶活性^[5]。Iturin A（0-100μM）处理Caco-2细胞48h，以浓度依赖性的方式抑制了细胞的生长，诱导了细胞凋亡，上调了凋亡基因bax的表达，下调了抗凋亡基因bcl-2的表达^[6]。

在体内，Iturin A（5, 10, 15mg/kg）通过尾静脉注射治疗肉瘤180细胞异种移植小鼠28天，显著抑制了肿瘤生长，诱导了肿瘤细胞凋亡，上调了Bax的表达，增加了caspase和PARP裂解，下调了CD31、Ki67、pAkt和pMAPK的表达^[7]。