Anisomycin(茴香霉素,AbMole,M5145)是一种由灰色链霉菌(Streptomyces griseolus)产生的吡咯烷类抗生素,在多种细胞和动物模型中展现出广泛的生物学效应。
在细胞水平上,Anisomycin(CAS No.:22862-76-6)以低至10 ng/mL的即可激活应激相关通路如JNK、p38 MAPK和ERK;而当浓度升至1 µg/mL时,则能显著抑制真核细胞蛋白质合成(降至对照组的46%),并诱导凋亡相关分子的释放,包括caspase-3、-8、-9的活化、eIF2α磷酸化及DNA断裂[1, 2]。在B16小鼠黑色素瘤细胞中,50 nM的
Anisomycin(茴香霉素,AbMole,M5145)即可抑制细胞球体生长,并下调葡萄糖代谢相关基因,同时上调p21、p53和TXNIP等生长抑制基因的mRNA表达[3];
Anisomycin(茴香霉素,AbMole,M5145)在非小细胞肺癌(NSCLC)细胞系中,通过抑制PI3K/Akt/mTOR通路发挥抗增殖作用,且与Cisplatin(顺铂)联用时可极大地阻断肿瘤生长[4]。Anisomycin(Flagecidin)在卵巢癌干细胞(CD44+/CD133+ HuOCSCs)中,处理后显著降低了ATP和总谷胱甘肽(T-GSH)含量,同时丙酮酸、脂质过氧化物(LPO)和丙二醛(MDA)的水平明显升高,提示Anisomycin还能诱导铁死亡[5]。在慢性髓系白血病(CML)CD34+干/祖细胞及Jurkat T细胞中,纳摩尔浓度的Anisomycin即可抑制增殖、自我更新与集落形成,并通过let-7c介导的JNK1/2–AP-1/STAT1/STAT3/Bim/Bcl-xL/Bax/Bak通路诱导凋亡[6]。在急性髓系白血病(AML)研究中,Anisomycin对FLT3-ITD突变细胞比FLT3野生型更敏感,其作用机制与线粒体复合物I活性的抑制、呼吸链功能障碍、ATP下降及氧化应激相关,而缺乏线粒体呼吸功能的细胞则对
Anisomycin(茴香霉素,AbMole,M5145)产生抗性[7]。在三阴性乳腺癌(TNBC)细胞系中,Anisomycin(茴香霉素)显著抑肿瘤生长,并通过破坏线粒体膜电位、降低ATP水平激活AMPK、抑制mTOR信号[8]。
在动物模型方面,Anisomycin(Wuningmeisu C)在3xTg-AD转基因小鼠中经灌胃给药可减轻脑内小胶质细胞和星形胶质细胞的活化,发挥神经保护作用,其潜在靶点富集于炎症通路[9];在NSCLC、AML、TNBC及黑色素瘤的异种移植小鼠模型中,Anisomycin(Flagecidin)均能有效抑制肿瘤生长,且未观察到明显毒性[10]。此外,在斑马鱼侧线发育模型中,暴露于Anisomycin后能诱导毛细胞死亡并抑制支持细胞的增殖[11];此外,在小鼠模型中,Anisomycin能提升骨矿化结节形成率及骨钙素(OCN)水平[12]。
综上,
Anisomycin(茴香霉素,AbMole,M5145)通过调控蛋白质合成、线粒体功能、MAPK信号、PI3K/Akt/mTOR通路、铁死亡等多重机制,在多种细胞系及小鼠、斑马鱼等动物模型中展现出复杂的生物学调控作用,是研究细胞应激、凋亡、衰老、代谢重编程及干细胞的有力工具。
参考文献及鸣谢
[1] Schipp, R.; Varga, J.; Bator, J.; et al. The Effect of a Dominant Inhibitory p53 Protein on Stress Responses Induced by Toxic and Non-Toxic Concentrations of Anisomycin in PC12 Cells.
Biology 2025,
14 (12).
[2] Scavuzzo, C. J.; LeBlancq, M. J.; Nargang, F.; et al. The amnestic agent anisomycin disrupts intrinsic membrane properties of hippocampal neurons via a loss of cellular energetics.
Journal of neurophysiology 2019,
122 (3), 1123-1135.
[3] Ushijima, H.; Monzaki, R.; Onodera, A. Suppressive Effects of Anisomycin on the Proliferation of B16 Mouse Melanoma Cells In Vitro.
Anticancer research 2021,
41 (12), 6113-6121.
[4] Tan, H.; Hu, B.; Xie, F.; et al. Anisomycin sensitizes non-small-cell lung cancer cells to chemotherapeutic agents and epidermal growth factor receptor inhibitor via suppressing PI3K/Akt/mTOR.
Fundamental & clinical pharmacology 2021,
35 (5), 822-831.
[5] Nie, X.; Chen, H.; Xiong, Y.; et al. Anisomycin has a potential toxicity of promoting cuproptosis in human ovarian cancer stem cells by attenuating YY1/lipoic acid pathway activation.
Journal of Cancer 2022,
13 (14), 3503-3514.
[6] Li, Y.; Hu, J.; Song, H.; et al. Antibiotic anisomycin selectively targets leukemia cell lines and patient samples through suppressing Wnt/beta-catenin signaling.
Biochemical and biophysical research communications 2018,
505 (3), 858-864.
[7] Zhang, C.; Deng, Q.; Bao, S.; et al. Anisomycin is active in preclinical models of pediatric acute myeloid leukemia via specifically inhibiting mitochondrial respiration.
Journal of bioenergetics and biomembranes 2021,
53 (6), 693-701.
[8] Yang, W.; Zhou, C.; Sun, Q.; et al. Anisomycin inhibits angiogenesis, growth, and survival of triple-negative breast cancer through mitochondrial dysfunction, AMPK activation, and mTOR inhibition.
Canadian journal of physiology and pharmacology 2022,
100 (7), 612-620.
[9] Jiao, J. J.; Hu, Y.; Cui, Y. J.; et al. Anisomycin alleviates cognitive impairments and pathological features in 3xTg-AD mice.
Neuropharmacology 2024,
261, 110159.
[10] Ushijima, H.; Horyozaki, A.; Maeda, M. Anisomycin-induced GATA-6 degradation accompanying a decrease of proliferation of colorectal cancer cell.
Biochemical and biophysical research communications 2016,
478 (1), 481-485.
[11] Yuan, X.; Qin, Y.; Wang, J.; et al. Anisomycin induces hair cell death and blocks supporting cell proliferation in zebrafish lateral line neuromast.
Comparative biochemistry and physiology. Toxicology & pharmacology : CBP 2021,
247, 109053.
[12] Xu, Y.; Gu, Y.; Ji, W.; et al. Activation of the extracellular-signal-regulated kinase (ERK)/c-Jun N-terminal kinase (JNK) signal pathway and osteogenic factors in subchondral bone of patients with knee osteoarthritis.
Annals of translational medicine 2021,
9 (8), 663.
细胞实验参考
细胞系:MDA-MB-468 cells
方法:Cells (1 × 106 cells per group) were treated with ANS for 24 h. Floating and adherent cells were harvested and centrifuged (300
g, 5 min).
浓度: 3μM
处理时间:24 h
参考文献:Biochem Biophys Res Commun. 2014 Jan 10;443(2):761-7.
* 上述方法来自公开文献,仅供相同目的实验参考。如实验目的、材料、方法不同,请参考其他文献。
动物实验参考
动物模型:C57BL/6 mice
配制:Not mentioned PBS
剂量:20 mg/kg
给药处理:Intraperitoneal injection
参考文献:Mol Med. 2021 Dec 4;27(1):152.
* 上述方法来自公开文献,仅供相同目的实验参考。如实验目的、材料、方法不同,请参考其他文献。
体内实验的工作液,建议现用现配,当天使用;如在配制过程中出现沉淀、析出现象,可以通过超声和(或)加热的方式助溶。
切勿一次性将产品全部溶解。
建议制定动物给药及实验方案时,尽量参考已发表的相关实验文献(溶剂种类及配比众多,简单地溶解目的化合物,并不能解决动物给药依从性、体内生物利用度、组织分布等相关问题,未必能保证目的化合物在动物体内充分发挥生物学效用)。