Environmentally relevant concentrations of niclosamide disrupt antioxidant defense, histology, and the liver and intestine transcriptome of Chinese soft-shelled turtle
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PROVIDER: PRJNA936854 | ENA |
REPOSITORIES: ENA
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Project description:To investigate the cellular responses of the Chinese soft-shelled turtle after niclosamide exposure, a total of 45 healthy juvenile turtles randomly selected and divided into three groups containing one control group (without NIC exposure, CG) and two experimental groups (exposed to 10 and 50 μg/L of NIC, respectively).
2024-01-01 | GSE225631 | GEO
Project description:The gene expression profile in treated CP70 side population spheroid cells (CP70sps cells) was analyzed to investigate the effect of niclosamide inhibition on ovarian tumor-initiating cells. CP70sps cells are isolated and characterized as one kind of ovarian tumor-initiating cells, and they show stemness properties and drug resistance capacity. According gene expression profiles and mechanistic analysis, all evidences revealed niclosamide disrupted multiple metabolic pathways affecting biogenetics, biogenesis and redox regulation. These studies support niclosamide as a promising therapeutic agent for ovarian cancer. CP70sps cells were treated with niclosamide for 0, 2, 4 and 6 hours respectively, and then cells were harvested and analyzed their gene expression profiles.
2012-08-05 | E-GEOD-36259 | biostudies-arrayexpress
Project description:In order to understanding the mechanisms of action of niclosamide, the active ingredient in the molluscicides, we used a Biomphalaria glabrata oligonucleotide microarray to investigate the effect of three sublethal exposures to niclosamide on the transcriptional responses of the snail B. glabrata relative to untreated snails. In addition to inducing biotransformation activity and inducing stress responses, niclosamide exposures also resulted in altered function of vesicle trafficking and may affect the snail’s oxygen binding capacity. In order to reveal how sublethal exposures of niclosamide to the snail B. glabrata affects the snail’s gene expression. The three sublethal doses of niclosamide tested are 0.15 mg/L (dose 1), 0.10 mg/L (dose 2), and 0.05 mg/L (dose 3). The control snails did not exposed to the niclosamid (0%). The snails were exposed to a given dose for 24 hours. Twenty live snails from each dose or control group were collected and randomly divided into four replicate groups, each with five snails, for subsequent RNA extraction and transcriptome analysis
2015-07-23 | E-GEOD-71223 | biostudies-arrayexpress
Project description:The gene expression profile in treated CP70 side population spheroid cells (CP70sps cells) was analyzed to investigate the effect of niclosamide inhibition on ovarian tumor-initiating cells. CP70sps cells are isolated and characterized as one kind of ovarian tumor-initiating cells, and they show stemness properties and drug resistance capacity. According gene expression profiles and mechanistic analysis, all evidences revealed niclosamide disrupted multiple metabolic pathways affecting biogenetics, biogenesis and redox regulation. These studies support niclosamide as a promising therapeutic agent for ovarian cancer.
2012-08-06 | GSE36259 | GEO
Project description:ALS is a complex neurodegenerative disease influenced by genetic, epigenetic, and environmental factors, resulting in dysfunction in cellular and molecular pathways. The limited efficacy of current treatments highlights the need for combination therapies targeting multiple aspects of the disease. Niclosamide, an anthelminthic drug listed as an essential medicine, has been repurposed in clinical trials due to its anti-inflammatory and anti-fibrotic properties. Niclosamide can inhibit various molecular pathways (such as STAT3 and mTOR) that are dysregulated in ALS, suggesting its potential to disrupt these altered mechanisms associated with the pathology. Our recent findings have demonstrated that niclosamide can effectively inhibit inflammatory and fibrotic molecular pathways in ALS models. We administered niclosamide intraperitoneally to two transgenic murine models, FUS and SOD1-G93A mice, which replicate key pathologies and biological processes of ALS. The treatment was initiated at the onset of symptoms, and we assessed the progression of the disease by neurological scores, rotarod and grip tests, as well as monitoring survival. Additionally, we examined the effects of the treatment on spinal cord and muscle degeneration in the treated mice. In both models, the administration of niclosamide resulted in a slowdown of disease progression, an increase in survival rates, and an improvement in tissue pathology. This was characterized by a reduction in gliosis, motor neuron loss, muscle atrophy, and inflammatory markers. Based on these results, our findings demonstrate that niclosamide can impact multiple pathways involved in ALS. This multi-targeted approach leads to a slowdown in the progression of the disease, thereby positioning niclosamide as a promising candidate for repurposing in the treatment of ALS.
2024-05-09 | GSE249071 | GEO
Project description:Because niclosamide inhibits growth and progression of endometriotic lesions, we performed RNA-seq in order to identify genes whose expression is regulated by niclosamide in endometriotic lesions. Our results shown that niclosamide modulates several genes related to cell signaling, extracellular matrix, and inflammatory signaling.
2017-01-01 | GSE79698 | GEO
Project description:Neuroblastoma is a pediatric tumor of the peripheral sympathetic nervous system with diverse clinical behaviors. Even with multimodal therapies, high-risk neuroblastoma has an unfavorable outcome irrespective of MYCN amplification, a well-established oncogenic driver in neuroblastoma pathogenesis, and its genetic heterogeneity has largely impeded efforts to correlate molecular targets with biological consequences for more effective treatment strategies. Here, using a gene expression-based approach, we identified the FDA-approved anthelmintic niclosamide as a potential anti-neuroblastoma drug. By combining the gene expression signature associated with high-risk neuroblastoma and the recurrent drug−transcript relationships inferred from up to one million perturbational gene expression profiles, our algorithm predicted effective therapeutic candidates by evaluating the extent to which a given compound or their combinations could ‘reverse’ the high-risk signature. Furthermore, we performed quantitative polymerase chain reaction (qPCR) to validate top five candidate reverse genes which are involved in DNA replication, including cyclin A2 (CCNA2), minichromosome maintenance 10 replication initiation factor (MCM10), ERCC excision repair 6 like, spindle assembly checkpoint helicase (ERCC6L), kinesin family member 20A (KIF20A), and RuvB like AAA ATPase 1 (RUVBL1). Indeed, those five genes were downregulated in niclosamide-treated cells, indicating niclosamide suppressed DNA replication and then inhibited cell proliferation. Using cell proliferation and clonogenic assays as well as flow cytometry, we determined the cytotoxic effects of niclosamide in MYCN-amplified SK-N-DZ and non-amplified SK-N-AS cells. The results showed that niclosamide could effectively reduce not only cell proliferation and colony formation but also trigger cell cycle arrest and apoptosis. Moreover, we conducted human tumor xenografts in a nude mice model to evaluate the in vivo efficacy of niclosamide and found that it significantly suppressed tumor growth and prolonged survival rate, but doesn’t cause organ damage and change body weight. To explore the molecular mechanism of niclosamide, stable-isotope dimethyl labeling strategy for quantitative proteomics was performed on both cell-based or xenograft-based MYCN-amplified SK-N-DZ and MYCN-nonamplified SK-N-AS models. We confirmed niclosamide not only mediated the function of mitochondrial electron transport chain but also the other functions in high risk neuroblastoma cell lines and xenografts. The results suggest that our developed expression-based strategy is useful for drug discovery and provides the possibility of repurposing the anthelminthic drug niclosamide for treating high-risk neuroblastoma therapy.
2022-02-23 | PXD010745 | Pride
Project description:Transcriptional states of peritoneal immune cells altered by induction of endometriosis-like lesions and niclosamide treatment
2022-11-14 | GSE147024 | GEO
Project description:In order to understanding the mechanisms of action of niclosamide, the active ingredient in the molluscicides, we used a Biomphalaria glabrata oligonucleotide microarray to investigate the effect of three sublethal exposures to niclosamide on the transcriptional responses of the snail B. glabrata relative to untreated snails. In addition to inducing biotransformation activity and inducing stress responses, niclosamide exposures also resulted in altered function of vesicle trafficking and may affect the snail’s oxygen binding capacity.
2015-07-23 | GSE71223 | GEO
Project description:Hepatocellular carcinoma (HCC) is a fatal malignancy with a dismal prognosis. The recent advances in genomics and transcriptomics have led to large volumes of molecular data for HCC, providing an unprecedented opportunity to translate these data into more effective therapeutics. By creating HCC gene expression signatures and comparing with drug response signatures from multiple datasets, we identified four antihelminthics (from over 1000 FDA-approved drugs) that can reverse the HCC disease gene expression. Among these four, niclosamide was the top hit, which we further evaluated in clinically relevant HCC cell lines and patient-derived xenografts (PDX). Given the poor water-solubility and limited systemic bioavailability of niclosamide, we also evaluated its ethanolamine salt (NEN), which has improved solubility and bioavailability. Both niclosamide and NEN significantly inhibited HCC cell proliferation in vitro, which was associated with down-regulation of key proteins involved in the AKT-mTOR, Wnt, Stat3, and EGFR/Ras/Raf signaling pathways. NEN additionally decreased the growth of three PDX models after oral administration (1,5000 ppm in food) for 4-6 weeks. Expression profiling demonstrated that niclosamide and NEN induced highly similar gene expression changes in HepG2 cells and in PDX models, and that both compounds significantly reversed HCC gene expression in vitro and in vivo . Our results suggest that NEN may be a preferred drug candidate for the treatment of HCC.
2017-03-01 | GSE77322 | GEO