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BioMed Research International 2013In this paper structural and microbiological studies on the ionophorous antibiotic monensin A and its derivatives have been collected. Monensin A is an ionophore which... (Review)
Review
In this paper structural and microbiological studies on the ionophorous antibiotic monensin A and its derivatives have been collected. Monensin A is an ionophore which selectively complexes and transports sodium cation across lipid membranes, and therefore it shows a variety of biological properties. This antibiotic is commonly used as coccidiostat and nonhormonal growth promoter. The paper focuses on both the latest and earlier achievements concerning monensin A antimicrobial activity. The activities of monensin derivatives, including modifications of hydroxyl groups and carboxyl group, are also presented.
Topics: Amides; Anti-Infective Agents; Cations; Coccidiostats; Crystallography, X-Ray; Drug Design; Ionophores; Microbial Sensitivity Tests; Molecular Structure; Monensin; Protein Conformation; Structure-Activity Relationship
PubMed: 23509771
DOI: 10.1155/2013/742149 -
Scientific Reports Nov 2022Asthma is a common respiratory disease associated with airway hyperresponsiveness (AHR), airway inflammation and mast cell (MC) accumulation in the lung. Monensin, an...
Asthma is a common respiratory disease associated with airway hyperresponsiveness (AHR), airway inflammation and mast cell (MC) accumulation in the lung. Monensin, an ionophoric antibiotic, has been shown to induce apoptosis of human MCs. The aim of this study was to define the effect of monensin on MC responses, e.g., antigen induced bronchoconstriction, and on asthmatic features in models of allergic asthma. Tracheal segments from house dust mite (HDM) extract sensitized guinea pigs were isolated and exposed to monensin, followed by histological staining to quantify MCs. Both guinea pig tracheal and human bronchi were used for pharmacological studies in tissue bath systems to investigate the monensin effect on tissue viability and antigen induced bronchoconstriction. Further, an HDM-induced guinea pig asthma model was utilized to investigate the effect of monensin on AHR and airway inflammation. Monensin decreased MC number, caused MC death, and blocked the HDM or anti-IgE induced bronchoconstriction in guinea pig and human airways. In the guinea pig asthma model, HDM-induced AHR, airway inflammation and MC hyperplasia could be inhibited by repeated administration of monensin. This study indicates that monensin is an effective tool to reduce MC number and MCs are crucial for the development of asthma-like features.
Topics: Guinea Pigs; Humans; Animals; Mast Cells; Pyroglyphidae; Monensin; Asthma; Allergens; Inflammation; Disease Models, Animal
PubMed: 36344588
DOI: 10.1038/s41598-022-23486-1 -
Biomedicine & Pharmacotherapy =... Sep 2022Glioblastoma (GBM) remains the most frequently diagnosed primary malignant brain cancer in adults. Despite recent progress in understanding the biology of GBM, the...
Glioblastoma (GBM) remains the most frequently diagnosed primary malignant brain cancer in adults. Despite recent progress in understanding the biology of GBM, the clinical outcome for patients remains poor, with a median survival of approximately one year after diagnosis. One factor contributing to failure in clinical trials is the fact that traditional models used in GBM drug discovery poorly recapitulate patient tumors. Previous studies have shown that monensin (MON) analogs, namely esters and amides on C-26 were potent towards various types of cancer cell lines. In the present study we have investigated the activity of these molecules in GBM organoids, as well as in a host:tumor organoid model. Using a mini-ring cell viability assay we have identified seven analogs (IC = 91.5 ± 54.4-291.7 ± 68.8 nM) more potent than parent MON (IC = 612.6 ± 184.4 nM). Five of these compounds induced substantial DNA fragmentation in GBM organoids, suggestive of apoptotic cell death. The most active analog, compound 1, significantly reduced GBM cell migration, induced PARP degradation, diminished phosphorylation of STAT3, Akt and GSK3β, increased ɣH2AX signaling and upregulated expression of the autophagy associated marker LC3-II. To investigate the activity of MON and compound 1 in a tumor microenvironment, we developed human cerebral organoids (COs) from human induced pluripotent stem cells (iPSCs). The COs showed features of early developing brain such as multiple neural rosettes with a proliferative zone of neural stem cells (Nestin+), neurons (TUJ1 +), primitive ventricular system (SOX2 +/Ki67 +), intermediate zone (TBR2 +) and cortical plate (MAP2 +). In order to generate host:tumor organoids, we co-cultured RFP-labeled U87MG cells with fully formed COs. Compound 1 and MON reduced U87MG tumor size in the COs after four days of treatment and induced a significant reduction of PARP expression. These findings highlight the therapeutic potential of MON analogs towards GBM and support the application of organoid models in anti-cancer drug discovery.
Topics: Adult; Brain Neoplasms; Cell Line, Tumor; Glioblastoma; Humans; Induced Pluripotent Stem Cells; Monensin; Organoids; Poly(ADP-ribose) Polymerase Inhibitors; Tumor Microenvironment
PubMed: 36076555
DOI: 10.1016/j.biopha.2022.113440 -
Journal of Dairy Science Jun 2018The interaction of monensin and essential oil was hypothesized to suppress protozoa and methane production while maintaining normal rumen function. The objective of this...
The interaction of monensin and essential oil was hypothesized to suppress protozoa and methane production while maintaining normal rumen function. The objective of this study was to determine the effects of feeding monensin (MON) and CinnaGar (CIN, a commercial blend of cinnamaldehyde and garlic oil; Provimi North America, Brookville, OH) on ruminal fermentation characteristics. Continuous culture fermentors (n = 4) were maintained in 4 experimental periods in a 4 × 4 Latin square design. Four dietary treatments were arranged in a 2 × 2 factorial: (1) control diet, 37 g/d of dry matter (40 g/d at ∼92.5% dry matter) of a 50:50 forage:concentrate diet containing no additive; (2) MON at 11 g/909 kg of dry matter; (3) CIN at 0.0043% of dry matter; and (4) a combination of MON and CIN at the levels in (2) and (3). Treatment had no effects on protozoal populations, concentration of NHN, total N flow of effluent, production of total volatile fatty acids, or flows of conjugated linoleic acid and total C18 fatty acids. The MON decreased acetate:propionate ratio and biohydrogenation of both total C18 and 18:1 cis-9 but increased protozoal generation time, concentration of peptide, and flow of 18:1 trans-11. The MON tended to decrease protozoal counts in effluent and flow of 18:0 but tended to increase propionate production. The CIN decreased true organic matter digestibility and protozoal N flow of effluent but increased nonammonia, nonmicrobial N flow. The CIN tended to decrease protozoal counts, microbial N flow, and neutral detergent fiber digestibility but tended to increase biohydrogenation of total C18, 18:2, and 18:3. The CIN tended to increase isovalerate production. The MON and CIN tended to interact for increased methane production and bacterial N flow. A second experiment was conducted to determine the effects of MON and CIN on protozoal nitrogen and cell volume in vitro. Four treatments included (1) control (feed only), (2) feed + 0.0043% dry matter CIN, (3) feed + 2.82 μM MON, and (4) feed + CIN + MON at the same levels as in (2) and (3). With no interactions, MON addition decreased percentage of protozoa that were motile and tended to decrease cell volume at 6 h. The CIN did not affect cell count or other indicators of motility or volume at either 3 or 6 h. Under the conditions of our study, we did not detect an additive response for MON and CIN to decrease protozoal counts or methane production. A 3-dimensional method is suggested to better estimate protozoal cell volume.
Topics: Animal Feed; Animals; Diet; Digestion; Fermentation; Monensin; North America; Oils, Volatile; Protozoan Infections, Animal; Rumen
PubMed: 29605331
DOI: 10.3168/jds.2017-13646 -
Microbiology Spectrum Aug 2023Monkeypox virus (MPXV) infections in humans have historically been restricted to regions of endemicity in Africa. However, in 2022, an alarming number of MPXV cases were...
Monkeypox virus (MPXV) infections in humans have historically been restricted to regions of endemicity in Africa. However, in 2022, an alarming number of MPXV cases were reported globally, with evidence of person-to-person transmission. Because of this, the World Health Organization (WHO) declared the MPXV outbreak a public health emergency of international concern. The supply of MPXV vaccines is limited, and only two antivirals, tecovirimat and brincidofovir, approved by the U.S. Food and Drug Administration (FDA) for the treatment of smallpox, are currently available for the treatment of MPXV infection. Here, we evaluated 19 compounds previously shown to inhibit different RNA viruses for their ability to inhibit orthopoxvirus infections. We first used recombinant vaccinia virus (rVACV) expressing fluorescence (mScarlet or green fluorescent protein [GFP]) and luciferase (Nluc) reporter genes to identify compounds with antiorthopoxvirus activity. Seven compounds from the ReFRAME library (antimycin A, mycophenolic acid, AVN-944, pyrazofurin, mycophenolate mofetil, azaribine, and brequinar) and six compounds from the NPC library (buparvaquone, valinomycin, narasin, monensin, rotenone, and mubritinib) showed inhibitory activity against rVACV. Notably, the anti-VACV activity of some of the compounds in the ReFRAME library (antimycin A, mycophenolic acid, AVN-944, mycophenolate mofetil, and brequinar) and all the compounds from the NPC library (buparvaquone, valinomycin, narasin, monensin, rotenone, and mubritinib) were confirmed with MPXV, demonstrating their inhibitory activity against two orthopoxviruses. Despite the eradication of smallpox, some orthopoxviruses remain important human pathogens, as exemplified by the recent 2022 monkeypox virus (MPXV) outbreak. Although smallpox vaccines are effective against MPXV, access to those vaccines is limited. In addition, current antiviral treatment against MPXV infections is limited to the use of the FDA-approved drugs tecovirimat and brincidofovir. Thus, there is an urgent need to identify novel antivirals for the treatment of MPXV infection and other potentially zoonotic orthopoxvirus infections. Here, we show that 13 compounds, derived from two different libraries, previously found to inhibit several RNA viruses, also inhibit VACV. Notably, 11 compounds also displayed inhibitory activity against MPXV.
Topics: Humans; Mpox (monkeypox); Mycophenolic Acid; Smallpox; Antimycin A; Monensin; Rotenone; Valinomycin; Monkeypox virus; Antiviral Agents
PubMed: 37278625
DOI: 10.1128/spectrum.04745-22 -
Annals of Medicine Dec 2023Colorectal cancer is the third leading cause of death in patients with cancers in America. Monensin has represented anti-cancer effect on various human cancer cells. We...
BACKGROUND/AIMS
Colorectal cancer is the third leading cause of death in patients with cancers in America. Monensin has represented anti-cancer effect on various human cancer cells. We seek to investigate the effect of monensin on proliferation of human colorectal cancer cells and explore whether IGF1R signaling pathway is involved in anti-cancer mechanism of monensin.
METHODS
Cell proliferation and migration were assessed by crystal violet staining and cell wounding assay respectively. Cell apoptosis was analyzed by Hoechst 33258 staining and flow cytometry. Cell cycle progression was detected with the use of flow cytometry. Cancer-associated pathways were assessed with the use of pathway-specific reporters. Gene expression was detected by touchdown-quantitative real-time PCR. Inhibition of IGF1R was tested by immunofluorescence staining. Inhibition of IGF1R signaling was accomplished by adenovirus-mediated expression of IGF1.
RESULTS
We found that monensin not only effectively inhibited cell proliferation, cell migration as well as cell cycle progression, but also induced apoptosis and G1 arrest in human colorectal cancer cells. Monensin was shown to target multiple cancer-related signaling pathways such as Elk1, AP1, as well as Myc/max, and suppressed IGF1R expression increasing IGF1 in colorectal cancer cells.
CONCLUSION
Monensin could suppressed IGF1R expression increasing IGF1 in colorectal cancer cells. It has the potential to be repurposed as an anti-colorectal cancer agent, but further studies are still required to investigate the detailed mechanisms of monensin underlying its anti-cancer motion.Key MessagesMonensin inhibits the cell proliferation and the migration, induces apoptosis and inhibits cell cycle progression in human colorectal cancer cells.Monensin may exert anti-cancer activity by targeting multiple signaling pathways, including the IGF1R signaling pathway.Monensin has the potential to be repurposed as an anti-colorectal cancer agent.
Topics: Humans; Anti-Bacterial Agents; Apoptosis; Cell Line, Tumor; Cell Proliferation; Monensin; Neoplasms; Receptor, IGF Type 1; Signal Transduction; Colorectal Neoplasms
PubMed: 36896461
DOI: 10.1080/07853890.2023.2166980 -
Journal of Animal Science Dec 2022This study aimed to determine the viability of sporozoites from Eimeria bovis when exposed to sodium butyrate (SB), monensin (MON), or butyric acid (BA), and to...
Short Communication: effect of sodium butyrate, monensin, and butyric acid on the viability of Eimeria bovis sporozoites and their degree of damage to a bovine epithelial cell line.
This study aimed to determine the viability of sporozoites from Eimeria bovis when exposed to sodium butyrate (SB), monensin (MON), or butyric acid (BA), and to determine the effects of SB on sporozoite invasion of cells in comparison to MON as measured by the damage to a bovine epithelial cell line. To determine viability, isolated sporozoites were suspended in one of four treatments: control (CON) of cell culture medium alone, SB = 0.028 mg/mL suspended in control medium, MON = 0.01 mg/mL suspended in CON, and BA = 0.18 mg/mL suspended in CON. The number of live sporozoites was less for the MON and BA treatments compared to the CON and SB treatments. The number of dead sporozoites was similar regardless of treatment. There was a trend for treatment to affect the percent sporozoite viability. Control, SB and BA treatments were similar, while MON compared to control and SB had decreased percent viability. Results for MON, when compared to BA, were similar for percent viability. Lactate dehydrogenase (LDH) release was used to determine cellular damage to Madin Darby Bovine Kidney (MDBK) cells when exposed to E. bovis sporozoites in vitro. Cells were exposed to similar numbers of sporozoites and treated with: CON, SB = 0.028 mg/mL in control medium, MON = 0.01 mg/mL in control medium. Control LDH result (with sporozoites) was greater than both the SB and MON treatments while the LDH for SB and Mon and cells not exposed to sporozoites were similar. SB and MON were both shown to decrease cellular damage to MDBK cells as determined by decreased LDH release. SB has the potential to act as an anticoccidial alternative to MON.
Topics: Cattle; Animals; Eimeria; Monensin; Butyric Acid; Sporozoites; Epithelial Cells
PubMed: 36315476
DOI: 10.1093/jas/skac360 -
Sheng Wu Gong Cheng Xue Bao = Chinese... Jul 2022Biodegradation of antibiotic pollutants by microorganisms has received widespread attention, to which the identification of microorganisms capable of efficiently...
Biodegradation of antibiotic pollutants by microorganisms has received widespread attention, to which the identification of microorganisms capable of efficiently degrading antibiotics is a key. In this study, a strain DM-1 with high degradation capability was successfully isolated from monensin-contaminated chicken manure by using monensin as the sole carbon source. The strain was further identified basing on morphological, physiological and biochemical characteristics and 16S rRNA gene sequence-based phylogenetic analysis. The degradation efficiency of DM-1 for monensin was determined by HPLC post-column derivatization, and then the degradation conditions of DM-1 were optimized. DM-1 was identified as a strain of and named as DM-1. The optimal conditions for monensin degradation by strain DM-1 were pH 7.0, 30 ℃, and initial monensin concentration of 50 mg/L. The strain DM-1 degraded more than 87.51% of monensin at an initial concentration of 10 mg/L in 28 days, while only a slight decrease in monensin concentration was observed in the control without monensin-degrading strain. This study indicates that the strain DM-1 has a promising application prospect in the bioremediation of monensin-contaminated environment.
Topics: Bacteria; Biodegradation, Environmental; Monensin; Phylogeny; RNA, Ribosomal, 16S; Soil Microbiology
PubMed: 35871629
DOI: 10.13345/j.cjb.220155 -
Toxins Jun 2022Carboxylic ionophores, such as monensin, salinomycin and lasalocid, are polyether antibiotics used widely in production animals for the control of coccidiosis, as well...
Carboxylic ionophores, such as monensin, salinomycin and lasalocid, are polyether antibiotics used widely in production animals for the control of coccidiosis, as well as for the promotion of growth and feed efficiency. Although the benefits of using ionophores are undisputed, cases of ionophore toxicosis do occur, primarily targeting the cardiac and skeletal muscles of affected animals. The 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyl tetrazolium bromide (MTT) viability assay was used to determine the cytotoxicity of monensin, salinomycin and lasalocid on mouse skeletal myoblasts (C2C12). Immunocytochemistry and immunofluorescent techniques were, in turn, performed to investigate the effects of the ionophores on the microfilament, microtubule and intermediate filament, i.e., desmin and synemin networks of the myoblasts. Monensin was the most cytotoxic of the three ionophores, followed by salinomycin and finally lasalocid. Monensin and salinomycin exposure resulted in the aggregation of desmin around the nuclei of affected myoblasts. The synemin, microtubule and microfilament networks were less affected; however, vesicles throughout the myoblast's cytoplasm produced gaps within the microtubule and, to a limited extent, the synemin and microfilament networks. In conclusion, ionophore exposure disrupted desmin filaments, which could contribute to the myofibrillar degeneration and necrosis seen in the skeletal muscles of animals suffering from ionophore toxicosis.
Topics: Animals; Cytoskeletal Proteins; Desmin; Ionophores; Lasalocid; Mice; Monensin; Myoblasts; Pyrans
PubMed: 35878184
DOI: 10.3390/toxins14070447 -
Veterinary Medicine and Science Sep 2023Grazing in arid and semi-arid regions faces pregnant ewes with feed restrictions and hence affects the offspring muscle fibre characteristics. Using feed additives that...
Restricted maternal nutrition and supplementation of propylene glycol, monensin sodium and rumen-protected choline chloride during late pregnancy does not affect muscle fibre characteristics of offspring.
BACKGROUND
Grazing in arid and semi-arid regions faces pregnant ewes with feed restrictions and hence affects the offspring muscle fibre characteristics. Using feed additives that enhance nutrient availability during foetal muscle development is expected to alter offspring skeletal muscle characteristics.
OBJECTIVES
This study evaluated the effect of maternal restricted nutrition and supplementation of propylene glycol, monensin sodium and rumen-protected choline chloride on lamb's muscle fibre characteristics.
METHODS
Forty-eight Ghezel ewes were randomly allocated to one of six diets (N = 8) during the last 6 weeks of gestation: ad libitum feed intake (AL); restricted feeding (RF); restricted feeding containing propylene glycol (PG); restricted feeding containing propylene glycol and monensin sodium (MS); restricted feeding containing propylene glycol and rumen-protected choline chloride (RPC); restricted feeding containing propylene glycol, monensin sodium and rumen-protected choline chloride (PMC). The muscle samples were obtained from the semitendinosus muscle of 2-week-old male lambs (n = 5/treatment) via biopsy and were stained and classified as fibre types I, IIA and IIB.
RESULTS
Pre-parturient maternal feed restriction and administration of propylene glycol, monensin sodium and rumen-protected choline chloride had no significant effect on fibre-type composition, fibre density of muscle, muscle cross-sectional area and volume density of fibres (p > 0.05).
CONCLUSIONS
Either maternal dietary restriction or supplementation of nutrient flux-involved additives during late pregnancy did not alter muscle fibre development and had no short-term effects on muscle properties of the resulting offspring as myogenesis occurs in early and mid-gestation, not late gestation. Therefore, maternal nutrition may not be a problematic issue in sheep production in arid and semi-arid areas.
Topics: Pregnancy; Animals; Sheep; Female; Male; Monensin; Choline; Rumen; Propylene Glycol; Muscle Fibers, Skeletal; Dietary Supplements
PubMed: 37556348
DOI: 10.1002/vms3.1239