Background
Nigericin sodium salt is an electrically neutral K +/H + ionophore from Streptomyctus hygroscopicus an antibiotic that is lipophilic and selectively causes potassium to drain from the mitochondrial membrane[8,9]. Nigericin sodium salt is a NLRP3 activator[1].
Nigericin sodium salt inhibited the migration and invasion of H460 lung cancer cells[1]. Nigericin sodium salt (0.1-10 nM) has apparently a dual effect on cell volume, that is a shrinking effect at lower Nigericin sodium salt concentrations and a swelling effect at higher concentrations[2].Nigericin sodium salt exhibits higher toxicity on S18 cells than S26 cells, with IC50 of 2.03±0.55 μM and 4.77±2.35 μM, respectively. Nigericin sodium salt dramatically reduces the migration ability of S18 and HONE-1 cells[3]. Nigericin sodium salt exhibits toxicity for the HT29 and SW116 cell line with IC50 of 12.92±0.25 μmol and 15.86±0.18 μmol. Nigericin sodium salt also shows a decreased ability to form colonies under anchorage-independent conditions in a standard soft agar assay[4].Using a combination of live-cell imaging and biochemical approaches, prototypical NLRP3 stimuli, the potassium ionophore nigericin, or millimolar concentrations of ATP exert both NLRP3-independent and -dependent effects on macrophages that result in cytokine release and cell death[5].Treatment of MN9D cells with Nigericin sodium salt led to an increase of LC3-II and p62 levels with concomitant activation of caspase. Ultrastructural examination revealed accumulation of autophagic vacuoles and swollen vacuoles in nigericin-treated cells[7].
In mice, Ngericin significantly reduces tumor growth. Nigericin sodium salt markedly decreases Bmi-1 in vivo. Overexpression of Bmi-1 partially restores CSC content and metastatic ability of NPC cells under Nigericin sodium salt treatment. The downregulation of Bmi-1 may be involved in the inhibitory effect of Nigericin sodium salt on CSCs in NPC[3].Nigericin sodium salt exerts anticancer effects on human osteosarcoma cancer cells by directly targeting STAT3. Nigericin sodium salt can significantly inhibit tumor migration and invasion. Nigericin sodium salt inhibits tumor growth in a mouse osteosarcoma model[6].
尼杆菌素钠盐是一种来自湿地链霉菌的电中性K+/H+离子载体，它是一种亲脂性抗生素，可以选择性地导致钾从线粒体膜中流失[8,9]。尼杆菌素钠盐是NLRP3激活剂[1]。
Nigericin钠盐抑制了H460肺癌细胞的迁移和侵袭[1]。在较低浓度下（0.1-10 nM），Nigericin钠盐似乎对细胞体积有收缩作用，而在较高浓度下则具有膨胀作用[2]。 Nigericin钠盐对S18细胞的毒性比对S26细胞更高，IC50分别为2.03±0.55μM和4.77±2.35μM。 Nigericin钠盐显著降低了S18和HONE-1细胞的迁移能力[3]。 Nigericin钠盐对HT29和SW116细胞系表现出毒性，IC50分别为12.92±0.25 μmol 和15.86±0.18 μmol。 Nigericin钠盐还显示出在标准软琼脂糖酸试验中，在无锚定条件下形成集落的能力降低[4]。使用活体显微镜成像和生化方法相结合，原型NLRP3刺激物—— 钾离子载体nigericin或ATP 的毫摩尔浓度都会产生 NLRP3非依赖性和依赖性效应，并导致巨噬细胞释放细胞因子和死亡[5]。将MN9D细胞处理Nigericin钠盐后，LC3-II和p62水平增加，并伴随着caspase的激活。超微结构检查显示nigericin处理的细胞中有自噬泡和肿大的空泡积累[7]。
在小鼠中，Nigericin显著减少肿瘤生长。Nigericin钠盐明显降低体内的Bmi-1水平。在Nigericin钠盐治疗下，Bmi-1的过度表达部分恢复了NPC细胞的CSC含量和转移能力。Bmi-1的下调可能参与了Nigericin钠盐对NPC CSCs的抑制作用。[3] Nigericin钠盐通过直接靶向STAT3，在人类骨肉瘤癌细胞上发挥抗癌作用。 Nigericin钠盐可以显著抑制肿瘤迁移和侵袭，并且在小鼠骨肉瘤模型中抑制肿瘤生长。[6]
参考文献:
[1]: Yakisich JS, Azad N, et,al. Nigericin decreases the viability of multidrug-resistant cancer cells and lung tumorspheres and potentiates the effects of cardiac glycosides. Tumour Biol. 2017 Mar;39(3):1010428317694310. doi: 10.1177/1010428317694310. PMID: 28351327.
[2]: Bissinger R, Malik A, et,al. Triggering of Suicidal Erythrocyte Death by the Antibiotic Ionophore Nigericin. Basic Clin Pharmacol Toxicol. 2016 May;118(5):381-9. doi: 10.1111/bcpt.12503. Epub 2015 Nov 13. PMID: 26458067.
[3]: Deng CC, Liang Y, et,al. Nigericin selectively targets cancer stem cells in nasopharyngeal carcinoma. Int J Biochem Cell Biol. 2013 Sep;45(9):1997-2006. doi: 10.1016/j.biocel.2013.06.023. Epub 2013 Jul 4. PMID: 23831840.
[4]: Zhou HM, Dong TT, et,al. Suppression of colorectal cancer metastasis by nigericin through inhibition of epithelial-mesenchymal transition. World J Gastroenterol. 2012 Jun 7;18(21):2640-8. doi: 10.3748/wjg.v18.i21.2640. PMID: 22690072; PMCID: PMC3370000.
[5]: Heid ME, Keyel PA, et,al. Mitochondrial reactive oxygen species induces NLRP3-dependent lysosomal damage and inflammasome activation. J Immunol. 2013 Nov 15;191(10):5230-8. doi: 10.4049/jimmunol.1301490. Epub 2013 Oct 2. PMID: 24089192; PMCID: PMC3833073.
[6]: Yang Z, Xie J, et,al. Nigericin exerts anticancer effects through inhibition of the SRC/STAT3/BCL-2 in osteosarcoma. Biochem Pharmacol. 2022 Apr;198:114938. doi: 10.1016/j.bcp.2022.114938. Epub 2022 Jan 31. PMID: 35114189.
[7]: Lim J, Lee Y, et,al. Nigericin-induced impairment of autophagic flux in neuronal cells is inhibited by overexpression of Bak. J Biol Chem. 2012 Jul 6;287(28):23271-82. doi: 10.1074/jbc.M112.364281. Epub 2012 Apr 5. PMID: 22493436; PMCID: PMC3390606.
[8]: Fruth IA, Arrizabalaga G. Toxoplasma gondii: induction of egress by the potassium ionophore nigericin. Int J Parasitol. 2007 Dec;37(14):1559-67. doi: 10.1016/j.ijpara.2007.05.010. Epub 2007 Jun 9. PMID: 17618633; PMCID: PMC2221775.
[9]:Kucejova B, Kucej M, et,al. A screen for nigericin-resistant yeast mutants revealed genes controlling mitochondrial volume and mitochondrial cation homeostasis. Genetics. 2005 Oct;171(2):517-26. doi: 10.1534/genetics.105.046540. Epub 2005 Jul 14. PMID: 16020778; PMCID: PMC1456768.
Protocol
| Cell experiment [1]: |
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Cell lines
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H460 cells
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Preparation Method
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Migration and invasion assays were performed using cells serum-starved overnight. For migration assays, H-460 cells were seeded in Transwell inserts in RPMI 1640 with or without drugs or Nigericin sodium salt(1 uM). Inserts were placed in plates with RPMI 1640 containing 10% FBS in the presence of DMSO, or Nigericin sodium salt (1 uM). After 24 h, cell migration was quantified.
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Reaction Conditions
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1 μM Nigericin sodium salt for 24h
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Applications
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Nigericin sodium salt inhibited the migration and invasion of H460 lung cancer cells.
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| Animal experiment [2]: |
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Animal models
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Nude mice(S18 cells were injected near the scapula of the nude mice)
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Preparation Method
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The mice were randomly divided into four groups with six animals each. DDP (2.5 mg/kg) was injected intraperitoneally for five continuous days and Nigericin sodium salt (4 mg/kg) was administrated intraperitoneally every two days.
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Dosage form
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4 mg/kg Nigericin sodium salt every two days.
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Applications
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Nigericin sodium salt significantly reduced tumor growth.
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参考文献:
[1]. Yakisich JS, Azad N, et,al. Nigericin decreases the viability of multidrug-resistant cancer cells and lung tumorspheres and potentiates the effects of cardiac glycosides. Tumour Biol. 2017 Mar;39(3):1010428317694310. doi: 10.1177/1010428317694310. PMID: 28351327.
[2]. Deng CC, Liang Y, et,al. Nigericin selectively targets cancer stem cells in nasopharyngeal carcinoma. Int J Biochem Cell Biol. 2013 Sep;45(9):1997-2006. doi: 10.1016/j.biocel.2013.06.023. Epub 2013 Jul 4. PMID: 23831840.
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