Nigericin |
| Catalog No.GC39719 |
K+/H+ ionophore,promoting K+/H+ exchange across mitochondrial membrane
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.:28380-24-7
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Nigericin is an antibiotic derived from Streptomyces hygroscopicus that act as a K+/H+ ionophore, promoting K+/H+ exchange across mitochondrial membranes[1].Nigericin can be a NLRP3 activator that induces the release of IL-1β as a NALP3-dependent manner[2]. Nigericin triggers eryptosis, an effect paralleled by ROS formation, and in part due to induction of oxidative stress. Nigericin triggers apoptosis[3].
[1]. Zotova L, et al. Novel components of an active mitochondrial K(+)/H(+) exchange. J Biol Chem. 2010 May 7;285(19):14399-414. [2]. Mariathasan S, et al.Cryopyrin activates the inflammasome in response to toxins and ATP.Nature. 2006 Mar 9;440(7081):228-32. [3]. Bissinger R, et al. Triggering of Suicidal Erythrocyte Death by the Antibiotic Ionophore Nigericin. Basic Clin Pharmacol Toxicol. 2016 May;118(5):381-9.
| Cas No. | 28380-24-7 | SDF | |
| Canonical SMILES | C[C@H]1[C@](O[C@@H]2C[C@](CC[C@@H]3C)([H])O[C@@]3([H])[C@@H](C)C(O)=O)([C@@H]([C@H](OC)C2)C)O[C@](C)([C@]4([H])O[C@](C)([C@]5([H])O[C@]([C@@]([C@H](C[C@H]6C)C)([H])O[C@@]6(O)CO)([H])C[C@@H]5C)CC4)C1 | ||
| Formula | C40H68O11 | M.Wt | 724.96 |
| Solubility | 1.2mg/mL in DMF, 20mg/mL in Ethanol | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
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Nigericin exerts anticancer effects through inhibition of the SRC/STAT3/BCL-2 in osteosarcoma
Biochem Pharmacol 2022 Apr;198:114938.PMID:35114189DOI:10.1016/j.bcp.2022.114938.
The treatment of osteosarcoma has reached a bottleneck period in recent 30 years, there is an urgent need to find new drugs and treatment methods. Nigericin, an antibiotic derived from Streptomyces hygroscopicus, has exerted promising antitumoral effect in various tumors. The anticancer effect of Nigericin in human osteosarcoma has never been reported. In the present study, we explored the anticancer effects of Nigericin in osteosarcoma in vitro and in vivo. Our results showed that Nigericin treatment significantly reduced tumor cell proliferation in dose-dependent and time-dependent in human osteosarcoma cells. Nigericin can inhibit cell growth of osteosarcoma cells, in addition to S-phase cycle arrest, the Nigericin induces apoptosis. Furthermore, bioinformatics predicted that Nigericin exerts anticancer effects through inhibiting SRC/STAT3 signaling pathway in osteosarcoma. The direct binding between SRC and activator of transcription 3 (STAT3) was confirmed by Western blot. Nigericin can down regulate STAT3 and Bcl-2. In order to further elucidate the inhibitory effect of Nigericin on SRC/STAT3/Bcl-2 signal transduction mechanism, we established human osteosarcoma cancer cells stably expressing STAT3. Western blot confirmed that Nigericin exerts anticancer effects on human osteosarcoma cancer cells by directly targeting STAT3. In addition, Nigericin can significantly inhibit tumor migration and invasion. Finally, Nigericin inhibits tumor growth in a mouse osteosarcoma model. The Nigericin targeting the SRC/STAT3/BCL-2 signaling pathway may provide new insights into the molecular mechanism of Nigericin on cancer cells and suggest its possible clinical application in osteosarcoma.
Dehydroepiandrosterone exacerbates nigericin-induced abnormal autophagy and pyroptosis via GPER activation in LPS-primed macrophages
Cell Death Dis 2022 Apr 19;13(4):372.PMID:35440074DOI:10.1038/s41419-022-04841-6.
As a widely acknowledged FDA-approved dietary supplement or over-the-counter medicines, dehydroepiandrosterone (DHEA) exerts anti-inflammatory and immunomodulatory function. Pyroptosis is an important form of programmed cell death (PCD), and which acts a key role in the body's anti-infection and inflammatory responses. But the effects and mechanisms of DHEA on pyroptosis remain unclear. Here, we found that DHEA inhibited the NLRP3 inflammasome components expression by blocking inflammatory signals in lipopolysaccharide (LPS)-primed macrophages, and prevented the bacterial toxin Nigericin (Nig)-induced NLRP3 inflammasome assembly. However, DHEA exacerbated NLRP3-independent cell death in Nig-treated inflammatory macrophages. During this process, DHEA induced the abnormal autophagy, which reflected as the blocking of autophagic flux and the accumulation of autophagy receptor p62 (SQSTM1) protein. In addition, DHEA caused a burst of reactive oxygen species (ROS) and activated extracellular signal-regulated kinase (ERK) phosphorylation in LPS plus Nig-stimulated macrophages but not in LPS-treated macrophages. Mechanistically, the present study certified that the activation of G protein-coupled estrogen receptor (GPER) signal mediated the cell death induced by DHEA in Nig-stimulated inflammatory macrophages, as GPER specific inhibitor G15 alleviated the abnormal autophagy and ultimately prevented the gasdermin D (GSDMD)-mediated pyroptosis induced by DHEA. Collectively, DHEA can exacerbate Nig-induced abnormal autophagy and pyroptosis via activation of GPER in LPS-primed macrophages, which prompts us the potential application value of DHEA in anti-infection or anti-tumor immunity.
Evidence of Nigericin as a potential therapeutic candidate for cancers: A review
Biomed Pharmacother 2021 May;137:111262.PMID:33508621DOI:10.1016/j.biopha.2021.111262.
Emerging studies have shown that Nigericin, an H+, K+ and Pb2+ ionophore, has exhibited a promising anti-cancer activity in various cancers. However, its anti-cancer mechanisms have not been fully elucidated. In this review, the recent progresses on the use of Nigericin in human cancers have been summarized. By exchanging H+ and K+ across cell membranes, Nigericin shows promising anti-cancer activities in in vitro and in vivo as a single agent or in combination with other anti-cancer drugs through decreasing intracellular pH (pHi). The underlying mechanisms of Nigericin also include the inactivation of Wnt/β-catenin signals, blockade of Androgen Receptor (AR) signaling, and activation of Stress-Activated Protein Kinase/c-Jun N-terminal Kinase (SAPK/JNK) signaling pathways. In many cancers, Nigericin is proved to specifically target putative Cancer Stem Cells (CSCs), and its synergistic effects on photodynamic therapy are also reported. Other mechanisms of Nigericin including influencing the mitochondrial membrane potentials, inducing an increase in drug accumulation and autophagy, controlling insulin accumulation in nuclei, and increasing the cytotoxic activity of liposome-entrapped drugs, are also discussed. Notably, the potential adverse effects such as teratogenic effects, insulin resistance and eryptosis shall not be ignored. Taken together, these reports suggest that treatment of cancer cells with Nigericin may offer a novel therapeutic strategy and future potential of translation to clinics.
Nigericin is effective against multidrug resistant gram-positive bacteria, persisters, and biofilms
Front Cell Infect Microbiol 2022 Dec 20;12:1055929.PMID:36605124DOI:10.3389/fcimb.2022.1055929.
Multidrug-resistant (MDR) bacteria pose a significant clinical threat to human health, but the development of antibiotics cannot meet the urgent need for effective agents, especially those that can kill persisters and biofilms. Here, we reported that Nigericin showed potent bactericidal activity against various clinical MDR Gram-positive bacteria, persisters and biofilms, with low frequencies of resistance development. Moreover, Nigericin exhibited favorable in vivo efficacy in deep-seated mouse biofilm, murine skin and bloodstream infection models. With Staphylococcus aureus, Nigericin disrupted ATP production and electron transport chain; cell death was associated with altered membrane structure and permeability. Obtaining nigericin-resistant/tolerant mutants required multiple rounds of challenge, and, cross-resistance to members of several antimicrobial classes was absent, probably due to distinct Nigericin action with the GraSR two-component regulatory system. Thus, our work reveals that Nigericin is a promising antibiotic candidate for the treatment of chronic or recurrent infections caused by Gram-positive bacteria.
Bavachin enhances NLRP3 inflammasome activation induced by ATP or Nigericin and causes idiosyncratic hepatotoxicity
Front Med 2021 Aug;15(4):594-607.PMID:33909257DOI:10.1007/s11684-020-0809-2.
Psoraleae Fructus (PF) is a well-known traditional herbal medicine in China, and it is widely used for osteoporosis, vitiligo, and other diseases in clinical settings. However, liver injury caused by PF and its preparations has been frequently reported in recent years. Our previous studies have demonstrated that PF could cause idiosyncratic drug-induced liver injury (IDILI), but the mechanism underlying its hepatotoxicity remains unclear. This paper reports that bavachin isolated from PF enhances the specific stimuli-induced activation of the NLRP3 inflammasome and leads to hepatotoxicity. Bavachin boosts the secretion of IL-1β and caspase-1 caused by ATP or Nigericin but not those induced by poly(I:C), monosodium urate crystal, or intracellular lipopolysaccharide. Bavachin does not affect AIM2 or NLRC4 inflammasome activation. Mechanistically, bavachin specifically increases the production of nigericin-induced mitochondrial reactive oxygen species among the most important upstream events in the activation of the NLRP3 inflammasome. Bavachin increases the levels of aspartate transaminase and alanine aminotransferase in serum and hepatocyte injury accompanied by the secretion of IL-1β via a mouse model of lipopolysaccharide-mediated susceptibility to IDILI. These results suggest that bavachin specifically enhances the ATP- or nigericin-induced activation of the NLRP3 inflammasome. Bavachin also potentially contributes to PF-induced idiosyncratic hepatotoxicity. Moreover, bavachin and PF should be evaded among patients with diseases linked to the ATP- or nigericin-mediated activation of the NLRP3 inflammasome, which may be a dangerous factor for liver injury.
Average Rating: 5 (Based on Reviews and 14 reference(s) in Google Scholar.)
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