Bethesda, MD 20894, Copyright Jin B, Wang C, Li J, Du X, Ding K, Pan J. Anthelmintic niclosamide disrupts the interplay of p65 and FOXM1/beta-catenin and eradicates leukemia stem cells in chronic myelogenous leukemia. FOIA Integrative modeling of open data identifies repurposed drug candidates for HCC, Figure 2. This site needs JavaScript to work properly. Unable to load your collection due to an error, Unable to load your delegates due to an error. 2020 Jul 24;12(8):2037. doi: 10.3390/cancers12082037. Careers. Intervening in β-catenin signaling by sulindac inhibits S100A4-dependent colon cancer metastasis. Abstract; Full Text; Full Text PDF; PubMed; Scopus (183) Google Scholar, 21. Potential mechanisms of action include degrading constitutively active androgen receptor splice variants (AR-Vs) or inhibiting other drug-resistance pathways (e.g., Wnt-signaling). 2009;28 Spec No Focus:F55-64. Prostate cancer. Singh AR, Joshi S, Burgoyne AM, Sicklick JK, Ikeda S, Kono Y, Garlich JR, Morales GA, Durden DL. The long-term effect of niclosamide on metastasis formation after discontinued treatment was quantified by scoring, and overall survival (n = 12 mice) was analyzed by Kaplan-Meier method after discontinuation of treatment. Niclosamide and NEN specifically reduced the viability of HCC cells: the agents were at least 7-fold more cytotoxic to HCCs than primary hepatocytes. Its ethanolamine salt, with greater bioavailability, was more effective than niclosamide at slowing the growth of genetically induced liver tumors and patient-derived xenografts in mice. The authors have declared that no conflict of interest exists. 2021 Mar 6;40:127906. doi: 10.1016/j.bmcl.2021.127906. However, advanced disease could become life-threatening, therefore, every stage prostate cancer should be controlled for the rest of the life to keep progression at bay. Regulation of TMEM16A by CK2 and Its Role in Cellular Proliferation. Published by Elsevier Inc. All rights reserved. Sack U, Walther W, Scudiero D, Selby M, Aumann J, Lemos C, Fichtner I, Schlag PM, Shoemaker RH, Stein U. Mol Biol Cell. Niclosamide was reported to have anti-tumor activities in multiple cancers, including liver cancer. Niclosamide may be taken on an empty stomach (either 1 hour before or 2 hours after a meal). Progression of colon cancer is particularly associated with metastasis formation. 2021 Feb 25;19(1):86. doi: 10.1186/s12967-021-02760-2. Epub 2016 Aug 5. Hilfenhaus G, Mompeón A, Freshman J, Prajapati DP, Hernandez G, Freitas VM, Ma F, Langenbacher AD, Mirkov S, Song D, Cho BK, Goo YA, Pellegrini M, Chen JN, Damoiseaux R, Iruela-Arispe ML. Cells were profiled using Illumina HumanHT-12 v4 Expression BeadChip. Niclosamide tablets should be thoroughly chewed or crushed and then swallowed with a small amount of water. A High-Content Screen Identifies Drugs That Restrict Tumor Cell Extravasation across the Endothelial Barrier. Mol Cancer Ther. Methods: Xing J, Shankar R, Drelich A, Paithankar S, Chekalin E, Dexheimer T, Rajasekaran S, Tseng CK, Chen B. bioRxiv. We evaluated the anti-tumor activity of niclosamide and its ethanolamine salt (NEN) in HCC cell lines (HepG2, Huh7, Hep3B, Hep40, and PLC/PRF/5), primary human hepatocytes, and 2 mouse models of HCC. Inhibition of the Wnt/β-catenin signaling pathway improves the anti-tumor effects of sorafenib against hepatocellular carcinoma. 2016 Nov;15(11):2553-2562. doi: 10.1158/1535-7163.MCT-15-0976. These findings identify niclosamide as a promising therapeutic adjunct to oxaliplatin chemotherapy. Niclosamide inhibits S100A4-induced metastasis formation in a mouse model of colon cancer and has therapeutic potential. Tomizawa M. Shinozaki F. Motoyoshi Y. et al. Oral administration of NEN to mice significantly slowed growth of genetically induced liver tumors and patient-derived xenografts, whereas niclosamide did not, coinciding with the observed greater bioavailability of NEN compared with niclosamide. Exp Mol Med. Klin Lab Diagn. In this experimental setting, niclosamide interfered in the Wnt signaling pathway by disrupting the complexation of β-catenin/TCF with the S100A4 promoter leading to reduced expression of S100A4 [ 13 ]. Effect of NEN in combination with sorafenib in PDX model, Figure 5. 2011 Jul 6;103(13):991-2. doi: 10.1093/jnci/djr221. Niclosamide displayed antitumor effects while not abrogating oxaliplatin efficacy. Aberrant overexpression of high mobility group AT-hook 2 (HMGA2) is frequently found in cancers and HMGA2 has been considered an anticancer therapeutic target. Reversal of Infected Host Gene Expression Identifies Repurposed Drug Candidates for COVID-19. Background & aims: Would you like email updates of new search results? screened a small molecule library that contained 2492 drugs approved for human use with a luciferase-coupled ATP quantitation assay to assess cell viability . Niclosamide is an oral chlorinated salicylanilide antihelminthic agent with potential anticancer activity suggested in several cancer types, however, … Epub 2011 Jul 27. Chin J Cancer. Methods: To identify a transcription inhibitor of S100A4, high-throughput screening of 1280 pharmacologically active compounds was performed using a human colon cancer cell line expressing a S100A4 promoter-driven luciferase (LUC) reporter gene construct (HCT116-S1004p-LUC). Privacy, Help In a bioinformatics search for agents that alter the HCC-specific gene expression pattern, we identified the anthelmintic niclosamide as a potential anti-tumor agent. 2014;13:800-11 17. Niclosamide suppresses migration of hepatocellular carcinoma cells and downregulates matrix metalloproteinase-9 expression. Similar results were obtained using other human colon cancer cell lines that exhibit increased levels of S100A4 (SW620, LS174T, SW480, and DLD-1). Niclosamide inhibits mTORC1 and ULK1 activities and induces LC3B expression in niclosamide-sensitive cell lines, but not in the niclosamide-resistant cell lines tested. Interestingly, niclosamide is a less effective inhibitor of Wnt-responsive … The potency of niclosamide on breast cancer was assessed in vitro and in vivo. Adrenocortical carcinoma is a rare aggressive endocrine cancer and surgical resection is the only effective therapy but has limited benefits . Niclosamide, an old antihelminthic agent, demonstrates antitumor activity by blocking multiple signaling pathways of cancer stem cells. Preprint. Cancer Lett. We identified niclosamide as anti-metastatic drug in colon cancer xenografted mice by restriction of liver metastases linked to shorter survival. 2013 Oct;(10):66-8, 34-7. Multi-targeted therapy of cancer by niclosamide: a new application for an old drug. National Library of Medicine Transcriptomics-Based Drug Repurposing Approach Identifies Novel Drugs against Sorafenib-Resistant Hepatocellular Carcinoma. Jang SG, Lee J, Hong SM, Song YS, Kim MJ, Kwok SK, Cho ML, Park SH. Effect of niclosamide on basal-like breast cancers. Niclosamide is an old anthelmintic drug that shows potential in fighting against cancers. Neoplasia. Using immunoprecipitation assays, we found NEN to bind cell division cycle 37 protein and disrupt its interaction with heat shock protein 90. Furthermore, niclosamide was also revealed to exert a synergistic effect with numerous cancer drugs in human cancer cells. Reverse correlation between HCC gene expression and niclosamide/NEN-mediated expression, Figure 6. For rare cancers, such as ACC, drug repositioning can play an essential role in finding a treatment for a disease that may otherwise be neglected due to high costs. Cancer Lett. (. Such studies with niclosamide have people involved and are approved by the National cancer institute. NEN binds to CDC37 and disrupts the HSP90/CDC37 interaction, National Library of Medicine Conclusions: 2021 Feb;16(2):728-753. doi: 10.1038/s41596-020-00430-z. Allgöwer C, Kretz AL, von Karstedt S, Wittau M, Henne-Bruns D, Lemke J. Based on gene expression signatures, we identified 3 anthelmintics that significantly altered the expression of genes that are up- or down-regulated in HCCs. Regan-Fendt K, Li D, Reyes R, Yu L, Wani NA, Hu P, Jacob ST, Ghoshal K, Payne PRO, Motiwala T. Cancers (Basel). Stein U, Arlt F, Smith J, Sack U, Herrmann P, Walther W, Lemm M, Fichtner I, Shoemaker RH, Schlag PM. Breast carcinoma is the most common female cancer with considerable metastatic potential. Androgens can cause the growth of prostate cancer cells. Niclosamide suppresses the expansion of follicular helper T cells and alleviates disease severity in two murine models of lupus via STAT3. In one model of HCC, liver tumor development was induced by hydrodynamic delivery of a sleeping beauty transposon expressing an activated form of Ras (v12) and truncated β-catenin (N90). The sensitivity of colorectal cancer cells to growth inhibition by niclosamide is correlated with autophagosome formation induced by niclosamide. In this study, a pan-cancer genomics survey based on Cancer Cell Line Encyclopedia (CCLE) and The Cancer Genome Atlas (TCGA) data indicated that HMGA2 was mainly overexpressed in gastrointestinal cancers including colorectal cancer. Tumor growth was monitored by bioluminescence imaging. Results: 2021 Feb 1;81(3):619-633. doi: 10.1158/0008-5472.CAN-19-3911. The combination of NEN and sorafenib was more effective at slowing growth of patient-derived xenografts than either agent alone. Niclosamide and cancer2.1. 8600 Rockville Pike Compared with the control group, discontinuation of treatment for 26 days showed reduced liver metastasis formation in mice (n = 6 mice per group) (control vs discontinuous treatment, mean metastasis score = 100% vs 34.9%, mean difference = 65.1%; 95% confidence interval [CI] = 18.4% to 111.9%, P < .01) and increased overall survival (n = 6 mice per group; control vs discontinuous treatment, median survival = 24 vs 46.5 days, ratio = 0.52, 95% CI = 0.19 to 0.84, P = .001). Zeng B, Glicksberg BS, Newbury P, Chekalin E, Xing J, Liu K, Wen A, Chow C, Chen B. Nat Protoc. Figure 1. However, this rate drastically drops to approximately 10% when distant metastases have formed a… 2020 Dec;52(12):1926-1935. doi: 10.1038/s12276-020-00540-4. 2012 Apr;31(4):178-84. doi: 10.5732/cjc.011.10290. Among the most common tumours in men, prostate malignancy is generally considered a slowly growing condition, which for many years remains without symptoms and metastasis. Keywords: Integrative modeling of open data…, Figure 1. Clinical trials are research studies that involve people. J Transl Med. Mol Cancer Ther; 16(2); 300-11. Accessibility COVID-19 is an emerging, rapidly evolving situation. Oral administration of NEN to mice significantly slowed growth of genetically induced liver tumors and patient-derived xenografts, whereas niclosamide did not, coinciding with the observed greater bioavailability of NEN compared with niclosamide. Pinto MC, Schreiber R, Lerias J, Ousingsawat J, Duarte A, Amaral M, Kunzelmann K. Cells. Effect of niclosamide and niclosamide…, Figure 2. Patients with nonmetastatic, local stage I tumors have a 5-year survival rate of 90%. Colon cancer is one of the most frequent causes of cancer death worldwide. 2016 Oct 10;381(1):58-66. doi: 10.1016/j.canlet.2016.07.013. J Natl Cancer Inst. Androgens such as testosterone can cause the growth of prostate cancer cells. In HepG2 cells and in patient-derived xenografts, administration of niclosamide or NEN increased expression of 20 genes down-regulated in HCC and reduced expression of 29 genes up-regulated in the 274-gene HCC signature. Cancers (Basel). COVID-19 is an emerging, rapidly evolving situation. 1. This phase I trial studies the side effects and best dose of niclosamide when given together with enzalutamide in treating patients with castration resistant prostate cancer that has spread from the primary site to other places in the body. The combination of NEN and sorafenib was more effective at slowing growth of patient-derived xenografts than either agent alone. Accessibility Interactions between tumor-derived proteins and Toll-like receptors. 8600 Rockville Pike Satoh et al. … Xenograft cells were harvested after 6 weeks treatment with NEN (1,500 p.p.m). Niclosamide: an established antihelminthic drug as a potential therapy against S100A4-mediated metastatic colon tumors. Bethesda, MD 20894, Copyright Niclosamide is a drug traditionally used in parasitic infections and has recently been shown to have an effect on the Wnt signaling pathway in cells. If niclosamide is being given to a young child, the tablets should be crushed to a fine powder … The Wnt pathway has particular importance in colorectal cancer. Mol Cancer Ther. Copyright © 2017 AGA Institute. Epub 2020 Nov 20. Wnt up your mind - intervention strategies for S100A4-induced metastasis in colon cancer. This is the final step to demonstrate whether a certain approach could be useful in treating a medical condition or not. We identified drugs that might specifically increase expression of genes that are down-regulated in HCCs and reduce expression of genes up-regulated in HCCs using a nonparametric, rank-based pattern-matching strategy based on the Kolmogorov-Smirnov statistic. Zhang Z, Zhou L, Xie N, Nice EC, Zhang T, Cui Y, Huang C. Signal Transduct Target Ther. Both agents disrupted interaction between cell division cycle 37 and heat shock protein 90 in HCC cells, with concomitant inhibition of their downstream signaling pathways. The effect of niclosamide on liver metastasis was assessed in a xenograft mouse model of human colon cancer (n = 8 mice) by in vivo imaging. Prevention and treatment information (HHS). Background Niclosamide, an FDA-approved anti-helminthic drug, has activity in preclinical models of castration-resistant prostate cancer (CRPC). Colon cancer cell lines (HCT116, SW620, LS174T, SW480, and DLD-1) were treated with 1 μM niclosamide to analyze the effect on S100A4 mRNA and protein expression by quantitative reverse transcription-polymerase chain reaction and immunoblot assays, and effects on cell migration, invasion, proliferation, and colony formation were also assessed in vitro.
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