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https://www.readbyqxmd.com/read/28137584/anthelminthic-drug-niclosamide-sensitizes-the-responsiveness-of-cervical-cancer-cells-to-paclitaxel-via-oxidative-stress-mediated-mtor-inhibition
#1
Liping Chen, Li Wang, Haibin Shen, Hui Lin, Dan Li
Drug repurposing represents an alternative therapeutic strategy to cancer treatment. The potent anti-cancer activities of a FDA-approved anthelminthic drug niclosamide have been demonstrated in various cancers. However, whether niclosamide is active against cervical cancer is unknown. In this study, we investigated the effects of niclosamide alone and its combination with paclitaxel in cervical cancer in vitro and in vivo. We found that niclosamide significantly inhibited proliferation and induced apoptosis of a panel of cervical cancer cell lines, regardless of their cellular origin and genetic pattern...
January 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28081501/isolation-characterization-using-lc-esi-qtof-nmr-and-in-vitro-cytotoxicity-assay-of-niclosamide-forced-degradation-products
#2
Johnsirani P, Vishnuvardhan Ch, Lingesh A, Naidu V G M, Naveen Ch, Satheeshkumar N
The present study describes the isolation, characterization and in vitro cytotoxic effect of all forced degradation products of niclosamide (NCM) an anthelmintic class of drug used specifically to treat tapeworms. NCM was subjected to forced degradation involving hydrolysis (acidic, alkaline and neutral), oxidative, photolysis and thermal stress, as per ICH (Q1A (R2)) suggested conditions. The drug under hydrolytic (acidic and basic) conditions showed extensive degradation, while it was stable under neutral hydrolytic, oxidative, photolytic and thermal stress conditions...
March 20, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28063518/role-of-nutraceutical-sirt1-modulators-in-ampk-and-mtor-pathway-evidence-of-a-synergistic-effect
#3
Luca Giovannini, Sara Bianchi
OBJECTIVE: The aim of this study was to evaluate the effect of different natural substances on SIRT1 expression and on AMPK and mTOR phosphorylation. Moreover, we investigated the presence of a synergistic effect between the substances. METHODS: Human cervical carcinoma cells were seeded in 12-well plates, then incubated with the nine tested substances (resveratrol, quercetin, berberine, catechin, tyrosol, ferulic acid, niclosamide, curcumin, and malvidin) at different concentrations and left in incubation for 3, 6, and 24 h...
February 2017: Nutrition
https://www.readbyqxmd.com/read/28054648/niclosamide-reduces-glucagon-sensitivity-via-hepatic-pka-inhibition-in-obese-mice-implications-for-glucose-metabolism-improvements-in-type-2-diabetes
#4
Md Kamrul Hasan Chowdhury, Nigel Turner, Nicholas L Bentley, Abhirup Das, Lindsay E Wu, Dulama Richani, Sonia Bustamante, Robert B Gilchrist, Margaret J Morris, Peter R Shepherd, Greg C Smith
Type 2 diabetes (T2D) is a global pandemic. Currently, the drugs used to treat T2D improve hyperglycemic symptom of the disease but the underlying mechanism causing the high blood glucose levels have not been fully resolved. Recently published data showed that salt form of niclosamide improved glucose metabolism in high fat fed mice via mitochondrial uncoupling. However, based on our previous work we hypothesised that niclosamide might also improve glucose metabolism via inhibition of the glucagon signalling in liver in vivo...
January 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28049163/correction-niclosamide-inhibits-androgen-receptor-variants-expression-and-overcomes-enzalutamide-resistance-in-castration-resistant-prostate-cancer
#5
(no author information available yet)
No abstract text is available yet for this article.
January 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27993848/mycobacterium-tuberculosis-is-selectively-killed-by-rifampin-and-rifapentine-in-hypoxia-at-neutral-ph
#6
Angelo Iacobino, Giovanni Piccaro, Federico Giannoni, Alessandro Mustazzolu, Lanfranco Fattorini
The activity of rifampin, rifapentine, bedaquiline, PA-824, clofazimine, nitazoxanide, isoniazid, amikacin, moxifloxacin, niclosamide, thioridazine and pyrazinamide was tested against nonreplicating (dormant) Mycobacterium tuberculosis under conditions of hypoxia at pH 5.8 and 7.3 mimicking environments of cellular granulomas and caseous granulomas, respectively. At pH 5.8, several drugs killed dormant bacilli, with the best being rifampin and rifapentine. At pH 7.3, only rifampin and rifapentine efficiently killed dormant bacilli while all other drugs showed little activity...
December 19, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27980107/niclosamide-inhibits-oxaliplatin-neurotoxicity-while-improving-colorectal-cancer-therapeutic-response
#7
Olivier Cerles, Evelyne Benoit, Christiane Chéreau, Sandrine Chouzenoux, Florence Morin, Marie-Anne Guillaumot, Romain Coriat, Niloufar Kavian, Thomas Loussier, Pietro Santulli, Louis Marcellin, Nathaniel E B Saidu, Bernard Weill, Frederic Batteux, Carole Nicco
Neuropathic pain is a limiting-factor of platinum-based chemotherapies. We sought to investigate the neuroprotective potential of niclosamide in peripheral neuropathies induced by oxaliplatin. Normal neuron-like and cancer cells were treated in vitro with oxaliplatin associated or not with an inhibitor of STAT3 and NF-кB, niclosamide. Cell production of reactive oxygen species and viability were measured by 2',7'-dichlorodihydrofluorescein diacetate and crystal violet. Peripheral neuropathies were induced in mice by oxaliplatin with or without niclosamide...
December 15, 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27939840/niclosamide-inhibits-lytic-replication-of-epstein-barr-virus-by-disrupting-mtor-activation
#8
Lu Huang, Mengtian Yang, Yan Yuan, Xiaojuan Li, Ersheng Kuang
Infection with the oncogenic γ-herpesviruses Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) cause several severe malignancies in humans. Inhibition of the lytic replication of EBV and KSHV eliminates the reservoir of persistent infection and transmission, consequently preventing the occurrence of diseases from the sources of infection. Antiviral drugs are limited in controlling these viral infectious diseases. Here, we demonstrate that niclosamide, an old anthelmintic drug, inhibits mTOR activation during EBV lytic replication...
February 2017: Antiviral Research
https://www.readbyqxmd.com/read/27888804/niclosamide-and-its-analogs-are-potent-inhibitors-of-wnt-%C3%AE-catenin-mtor-and-stat3-signaling-in-ovarian-cancer
#9
Rebecca C Arend, Angelina I Londoño-Joshi, Abhishek Gangrade, Ashwini A Katre, Chandrika Kurpad, Yonghe Li, Rajeev S Samant, Pui-Kai Li, Charles N Landen, Eddy S Yang, Bertha Hidalgo, Ronald D Alvarez, J Michael Straughn, Andres Forero, Donald J Buchsbaum
Epithelial ovarian cancer (EOC) is the leading cause of gynecologic cancer mortality worldwide. Platinum-based therapy is the standard first line treatment and while most patients initially respond, resistance to chemotherapy usually arises. Major signaling pathways frequently upregulated in chemoresistant cells and important in the maintenance of cancer stem cells (CSCs) include Wnt/β-catenin, mTOR, and STAT3. The major objective of our study was to investigate the treatment of ovarian cancer with targeted agents that inhibit these three pathways...
November 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27876936/in-vitro-and-in-vivo-anthelmintic-activity-of-seed-extract-of-coriandrum-sativum-compared-to-niclosamid-against-hymenolepis-nana-infection
#10
Samaneh Hosseinzadeh, Maryam Jamshidian Ghalesefidi, Mehdi Azami, Mohammad Ali Mohaghegh, Seyed Hossein Hejazi, Mohsen Ghomashlooyan
Phytotherapy can be an alternative for the control of gastrointestinal parasites in human and animals. Coriander (Coriandrum sativum L.) is a medicinal plant which grown as a spice crop all over the world. The seeds of this plant have been used to treat parasitic disease, indigestion, diabetes, rheumatism and pain in the joints. This study was carried out to compare the efficacy of Niclosamid and alcoholic seed extract of C. sativum on Hymenolepis nana infection, in vivo and vitro. For in vivo study, Balb/c mice were used, to compare the efficacy of 50 mg/kg body weight (B...
December 2016: Journal of Parasitic Diseases: Official Organ of the Indian Society for Parasitology
https://www.readbyqxmd.com/read/27872020/niclosamide-ethanolamine-inhibits-artery-constriction
#11
Shan-Liang Li, Jie Yan, Yan-Qiu Zhang, Chang-Lin Zhen, Ming-Yu Liu, Jing Jin, Jin-Lai Gao, Xiao-Lin Xiao, Xin Shen, Yu Tai, Nan Hu, Xin-Zi Zhang, Zhi-Jie Sun, De-Li Dong
We previously demonstrated that the typical mitochondrial uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP) inhibited artery constriction, but CCCP was used only as a pharmacological tool. Niclosamide is an anthelmintic drug approved by FDA. Niclosamide ethanolamine (NEN) is a salt form of niclosamide and has been demonstrated to uncouple mitochondrial oxidative phosphorylation. The aim of the present study was to elucidate the vasoactivity of NEN and the potential mechanisms. Isometric tension of rat mesenteric artery and thoracic aorta was recorded by using multi-wire myograph system...
January 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27793003/evaluation-of-quantitative-assays-for-the-identification-of-direct-signal-transducer-and-activator-of-transcription-3-stat3-inhibitors
#12
Steffanie L Furtek, Christopher J Matheson, Donald S Backos, Philip Reigan
In many forms of cancer the signal transducer and activator of transcription 3 (STAT3) transcription factor remains constitutively active, driving cancer survival and progression. The critical role of STAT3 in tumorigenesis has prompted a campaign of drug discovery programs to identify small molecules that disrupt the function of STAT3, with more recent efforts focusing on direct STAT3 inhibition. There are two target binding sites for direct STAT3 inhibitors: the SH2 dimerization domain and the DNA-binding domain...
October 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27742486/antiviral-activities-of-niclosamide-and-nitazoxanide-against-chikungunya-virus-entry-and-transmission
#13
Yu-Ming Wang, Jeng-Wei Lu, Chang-Chi Lin, Yuan-Fan Chin, Tzong-Yuan Wu, Liang-In Lin, Zheng-Zong Lai, Szu-Cheng Kuo, Yi-Jung Ho
Chikungunya disease results from an infection with the arbovirus, chikungunya virus (CHIKV). Symptoms of CHIKV include fever and persistent, severe arthritis. In recent years, several antiviral drugs have been evaluated in clinical trials; however, no registered antivirals have been approved for clinical therapy. In this study, we established a high-throughput screening (HTS) system based on CHIKV 26S mediated insect cell fusion inhibition assay. Our screening system was able to search potential anti-CHIKV drugs in vitro...
October 11, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27652012/niclosamide-suppresses-renal-cell-carcinoma-by-inhibiting-wnt-%C3%AE-catenin-and-inducing-mitochondrial-dysfunctions
#14
Juan Zhao, Qiushan He, Zhimin Gong, Sen Chen, Long Cui
PURPOSE: To investigate the effects of anthelminthic drug niclosamide in renal cell carcinoma (RCC) and the underlying mechanisms of its action. METHODS: The effects of niclosamide on the proliferation and apoptosis of RCC cells were examined in vitro and in vivo by using MTS, colony formation assay, flow cytometry and xenograft cancer mouse model. Mechanism studies were performed by analyzing Wnt/β-catenin signaling and mitochondrial functions in a panel of RCC cell lines...
2016: SpringerPlus
https://www.readbyqxmd.com/read/27633064/reprofiled-anthelmintics-abate-hypervirulent-stationary-phase-clostridium-difficile
#15
Major Gooyit, Kim D Janda
Prolonged use of broad-spectrum antibiotics disrupts the indigenous gut microbiota, which consequently enables toxigenic Clostridium difficile species to proliferate and cause infection. The burden of C. difficile infections was exacerbated with the outbreak of hypervirulent strains that produce copious amounts of enterotoxins and spores. In recent past, membrane-active agents have generated a surge of interest due to their bactericidal property with a low propensity for resistance. In this study, we capitalized on the antimicrobial property and low oral bioavailability of salicylanilide anthelmintics (closantel, rafoxanide, niclosamide, oxyclozanide) to target the gut pathogen...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27631130/niclosamide-is-a-negative-allosteric-modulator-of-group-i-metabotropic-glutamate-receptors-implications-for-neuropathic-pain
#16
Ni Ai, Richard D Wood, Eric Yang, William J Welsh
PURPOSE: Novel therapeutics are greatly needed that target specific pathological receptors and pathways involved in Neuropathic Pain (NP). Extending our previous work published in this Journal on Group I metabotropic glutamate receptor (mGluR) modulators, we now investigate the therapeutic potential of niclosamide in modulating aberrant glutamate transmission in NP. METHOD: Calcium mobilization assays and cross-receptor selectivity experiments are conducted to characterize the pharmacological activity of niclosamide...
September 8, 2016: Pharmaceutical Research
https://www.readbyqxmd.com/read/27613696/niclosamide-prevents-systemic-sclerosis-in-a-reactive-oxygen-species-induced-mouse-model
#17
Florence Morin, Niloufar Kavian, Carole Nicco, Olivier Cerles, Christiane Chéreau, Frédéric Batteux
Systemic sclerosis (SSc) is a connective tissue disorder characterized by fibrosis of the skin and inner organs, vasculopathy, and immunological abnormalities. Recent insights on the implication of STAT3, AKT, and Wnt/β-catenin in fibrosis have prompted us to investigate, in a mouse model of ROS-induced SSc, the effects of niclosamide, an antihelmintic drug that inhibits both of these signaling pathways. SSc was induced in BALB/c mice by daily s.c. injections of hypochlorous acid (HOCl). Mice were treated or not every other day, 5 d a week, for 6 wk, by niclosamide...
September 9, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27571349/identification-of-small-molecule-inhibitors-of-zika-virus-infection-and-induced-neural-cell-death-via-a-drug-repurposing-screen
#18
Miao Xu, Emily M Lee, Zhexing Wen, Yichen Cheng, Wei-Kai Huang, Xuyu Qian, Julia Tcw, Jennifer Kouznetsova, Sarah C Ogden, Christy Hammack, Fadi Jacob, Ha Nam Nguyen, Misha Itkin, Catherine Hanna, Paul Shinn, Chase Allen, Samuel G Michael, Anton Simeonov, Wenwei Huang, Kimberly M Christian, Alison Goate, Kristen J Brennand, Ruili Huang, Menghang Xia, Guo-Li Ming, Wei Zheng, Hongjun Song, Hengli Tang
In response to the current global health emergency posed by the Zika virus (ZIKV) outbreak and its link to microcephaly and other neurological conditions, we performed a drug repurposing screen of ∼6,000 compounds that included approved drugs, clinical trial drug candidates and pharmacologically active compounds; we identified compounds that either inhibit ZIKV infection or suppress infection-induced caspase-3 activity in different neural cells. A pan-caspase inhibitor, emricasan, inhibited ZIKV-induced increases in caspase-3 activity and protected human cortical neural progenitors in both monolayer and three-dimensional organoid cultures...
October 2016: Nature Medicine
https://www.readbyqxmd.com/read/27545321/defined-host-guest-chemistry-on-nanocarbon-for-sustained-inhibition-of-cancer
#19
Fatemeh Ostadhossein, Santosh K Misra, Prabuddha Mukherjee, Alireza Ostadhossein, Enrique Daza, Saumya Tiwari, Shachi Mittal, Mark C Gryka, Rohit Bhargava, Dipanjan Pan
Signal transducer and activator of transcription factor 3 (STAT-3) is known to be overexpressed in cancer stem cells. Poor solubility and variable drug absorption are linked to low bioavailability and decreased efficacy. Many of the drugs regulating STAT-3 expression lack aqueous solubility; hence hindering efficient bioavailability. A theranostics nanoplatform based on luminescent carbon particles decorated with cucurbit[6]uril is introduced for enhancing the solubility of niclosamide, a STAT-3 inhibitor. The host-guest chemistry between cucurbit[6]uril and niclosamide makes the delivery of the hydrophobic drug feasible while carbon nanoparticles enhance cellular internalization...
August 22, 2016: Small
https://www.readbyqxmd.com/read/27542212/computational-drugs-repositioning-identifies-inhibitors-of-oncogenic-pi3k-akt-p70s6k-dependent-pathways-among-fda-approved-compounds
#20
Diego Carrella, Isabella Manni, Barbara Tumaini, Rosanna Dattilo, Federica Papaccio, Margherita Mutarelli, Francesco Sirci, Carla A Amoreo, Marcella Mottolese, Manuela Iezzi, Laura Ciolli, Valentina Aria, Roberta Bosotti, Antonella Isacchi, Fabrizio Loreni, Alberto Bardelli, Vittorio E Avvedimento, Diego di Bernardo, Luca Cardone
The discovery of inhibitors for oncogenic signalling pathways remains a key focus in modern oncology, based on personalized and targeted therapeutics. Computational drug repurposing via the analysis of FDA-approved drug network is becoming a very effective approach to identify therapeutic opportunities in cancer and other human diseases. Given that gene expression signatures can be associated with specific oncogenic mutations, we tested whether a "reverse" oncogene-specific signature might assist in the computational repositioning of inhibitors of oncogenic pathways...
September 13, 2016: Oncotarget
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