• Journal of Life Science
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• v.24 no.7
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• pp.769-776
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• 2014

Anisomycin, also known as flagecidin, is an antibiotic produced by Streptomyces griseolus that inhibits protein synthesis by binding to the ribosomal 28S subunit. The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a protein that induces apoptotic cell death. TRAIL primarily causes apoptosis in tumor cells by binding to death receptors. Many human cancer cell lines are refractory to TRAIL-induced cell death. In this study, we investigated whether anisomycin could enhance TRAIL-mediated apoptosis in TRAIL-resistant human hepatocarcinoma Hep3B cells. Treatment with anisomycin and TRAIL alone did not reduce cell viability in Hep3B cells. However, in the presence of TRAIL, the anisomycin concentration dependently reduced the cell viability. Our results indicate that anisomycin sensitizes Hep3B cells to TRAIL-mediated apoptosis and that this occurs, at least partly, via caspase activation. Interestingly, Bid knockdown by small interfering RNA significantly reduced the induction of apoptosis in combination with anisomycin and TRAIL, indicating that anisomycin effectively acts to lower the threshold at which TRAIL-mediated truncated Bid triggers the mitochondrial-mediated apoptosis program in Hep3B cells. Therefore, the use of TRAIL in combination with anisomycin might provide an effective therapeutic strategy for the safe treatment of some TRAIL-resistant cancer cells.

• BMB Reports
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• v.54 no.11
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• pp.545-550
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• 2021

Anisomycin is known to inhibit eukaryotic protein synthesis and has been established as an antibiotic and anticancer drug. However, the molecular targets of anisomycin and its mechanism of action have not been explained in macrophages. Here, we demonstrated the anti-inflammatory effects of anisomycin both in vivo and in vitro. We found that anisomycin decreased the mortality rate of macrophages in cecal ligation and puncture (CLP)- and lipopolysaccharide (LPS)-induced acute sepsis. It also declined the gene expression of proinflammatory mediators such as inducible nitric oxide synthase, tumor necrosis factor-α, and interleukin-1β as well as the nitric oxide and proinflammatory cytokines production in macrophages subjected to LPS-induced acute sepsis. Furthermore, anisomycin attenuated nuclear factor (NF)-κB activation in LPS-induced macrophages, which correlated with the inhibition of phosphorylation of NF-κB-inducing kinase and IκB kinase, phosphorylation and IκBα proteolytic degradation, and NF-κB p65 subunit nuclear translocation. These results suggest that anisomycin prevented acute inflammation by inhibiting NF-κB-related inflammatory gene expression and could be a potential therapeutic candidate for sepsis.

• Bulletin of the Korean Chemical Society
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• v.20 no.3
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• pp.321-324
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• 1999

Anisomycin derivatives have been synthesized via syn-amidoalkylation followed by installation of p-methoxy-phenyl group and subsequent transformation.

• Applied Biological Chemistry
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• v.39 no.2
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• pp.153-158
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• 1996

During the screening of herbicidal substances from microbial secondary metabolites using photoautotrophic cells, a strain of ME-13 with strong herbicidal activity was isolated from soil. Based on the taxonomic studies, the strain was identified as Streptomyces. Two active compounds were purified from the culture broth through the column chromatographies using active charcoal, silica gel, MCI gel, and ODS HPLC. The compounds were identified as AB3217-A and B, respectively, related to anisomycin by spectroscopic methods. AB3217-A and B completely suppressed the germination of radish and barnyard grass at 25 ppm. In comparison to anisomycin, they showed the 6 times higher inhibitory activities against the growth of shoot and root of radish and barnyard grass with EC5O of around 6 ppm.

• Bulletin of the Korean Chemical Society
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• v.19 no.1
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• pp.37-38
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• 1998

• Molecular & Cellular Toxicology
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• v.5 no.4
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• pp.335-345
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• 2009

A major source of paeoniflorin (PF) which was from the Paeonia lactiflora root, has been used as a herbal medicine in East Asia for its antiallergic, antiinflammatory, and immunoregulatory effects. However, only few details are known about the mechanism of apoptosis induced by this compound. The present study was undertaken to further elucidate the molecular mechanism of apoptosis and the changes of gene expression elicited by PF using DNA microarrays and computational gene-expression analysis tools in human leukemia U937 cells. A comparative global transcription analysis between treatment with PF and anisomycin (AM) that induces apoptosis in U937 cells revealed that c-Jun-$NH_2$-kinase (JNK) pathway related genes were less expressed in PF-treated cells. Elucidation of the mechanisms by which PF conducts its anti-cancer activities through comparative analysis of the gene expression is necessary to provide a solid foundation for its use as a promising agent in prevention and treatment strategies.

• Journal of Ginseng Research
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• v.43 no.1
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• pp.95-104
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• 2019

Background: Oxidized low-density lipoprotein (ox-LDL) causes vascular endothelial cell inflammatory response and apoptosis and plays an important role in the development and progression of atherosclerosis. Ginsenoside compound K (CK), a metabolite produced by the hydrolysis of ginsenoside Rb1, possesses strong anti-inflammatory effects. However, whether or not CK protects ox-LDL-damaged endothelial cells and the potential mechanisms have not been elucidated. Methods: In our study, cell viability was tested using a 3-(4, 5-dimethylthiazol-2yl-)-2,5-diphenyl tetrazolium bromide (MTT) assay. Expression levels of interleukin-6, monocyte chemoattractant protein-1, tumor necrosis factor-${\alpha}$, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 were determined by enzyme-linked immunosorbent assay and Western blotting. Mitochondrial membrane potential (${\Delta}{\Psi}m$) was detected using JC-1. The cell apoptotic percentage was measured by the Annexin V/ propidium iodide (PI) assay, lactate dehydrogenase, and caspase-3 expression. Apoptosis-related proteins, nuclear factor $(NF)-{\kappa}B$, and mitogen-activated protein kinases (MAPK) signaling pathways protein expression were quantified by Western blotting. Results: Our results demonstrated that CK could ameliorate ox-LDL-induced human umbilical vein endothelial cells (HUVECs) inflammation and apoptosis, $NF-{\kappa}B$ nuclear translocation, and the phosphorylation of p38 and c-Jun N-terminal kinase (JNK). Moreover, anisomycin, an activator of p38 and JNK, significantly abolished the anti-apoptotic effects of CK. Conclusion: These results demonstrate that CK prevents ox-LDL-induced HUVECs inflammation and apoptosis through inhibiting the $NF-{\kappa}B$, p38, and JNK MAPK signaling pathways. Thus, CK is a candidate drug for atherosclerosis treatment.

• Biomolecules & Therapeutics
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• v.26 no.2
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• pp.121-129
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• 2018

Oxidized low-density lipoprotein (ox-LDL)-induced macrophage foam cell formation and apoptosis play critical roles in the pathogenesis of atherosclerosis. Thioredoxin-1 (Trx) is an antioxidant that potently protects various cells from oxidative stress-induced cell death. However, the protective effect of Trx on ox-LDL-induced macrophage foam cell formation and apoptosis has not been studied. This study aims to investigate the effect of recombinant human Trx (rhTrx) on ox-LDL-stimulated RAW264.7 macrophages and elucidate the possible mechanisms. RhTrx significantly inhibited ox-LDL-induced cholesterol accumulation and apoptosis in RAW264.7 macrophages. RhTrx also suppressed the ox-LDL-induced overproduction of lectin-like oxidized LDL receptor (LOX-1), Bax and activated caspase-3, but it increased the expression of Bcl-2. In addition, rhTrx markedly inhibited the ox-LDL-induced production of intracellular reactive oxygen species (ROS) and phosphorylation of p38 mitogen-activated protein kinases (MAPK). Furthermore, anisomycin (a p38 MAPK activator) abolished the protective effect of rhTrx on ox-LDL-stimulated RAW264.7 cells, and SB203580 (a p38 MAPK inhibitor) exerted a similar effect as rhTrx. Collectively, these findings indicate that rhTrx suppresses ox-LDL-stimulated foam cell formation and macrophage apoptosis by inhibiting ROS generation, p38 MAPK activation and LOX-1 expression. Therefore, we propose that rhTrx has therapeutic potential in the prevention and treatment of atherosclerosis.