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Niclosamide Suppresses Cancer Cell Growth By Inducing Wnt Co-Receptor LRP6 Degradation and Inhibiting the Wnt/β-Catenin Pathway
Open accessAbstract
The Wnt/β-catenin signaling pathway is important for tumor initiation and progression. The low density lipoprotein receptor-related protein-6 (LRP6) is an essential Wnt co-receptor for Wnt/β-catenin signaling and represents a promising anticancer target. Recently, the antihelminthic drug, niclosamide was found to inhibit Wnt/β-catenin signaling, although the mechanism was not well defined. We found that niclosamide was able to suppress LRP6 expression and phosphorylation, block Wnt3A-induced β-catenin accumulation, and inhibit Wnt/β-catenin signaling in HEK293 cells. Furthermore, the inhibitory effects of niclosamide on LRP6 expression/phosphorylation and Wnt/β-catenin signaling were conformed in human prostate PC-3 and DU145 and breast MDA-MB-231 and T-47D cancer cells. Moreover, we showed that the mechanism by which niclosamide suppressed LRP6 resulted from increased degradation as evident by a shorter half-life. Finally, we demonstrated that niclosamide was able to induce cancer cell apoptosis, and displayed excellent anticancer activity with IC(50) values less than 1 µM for prostate PC-3 and DU145 and breast MDA-MB-231 and T-47D cancer cells. The IC(50) values are comparable to those shown to suppress the activities of Wnt/β-catenin signaling in prostate and breast cancer cells. Our data indicate that niclosamide is a unique small molecule Wnt/β-catenin signaling inhibitor targeting the Wnt co-receptor LRP6 on the cell surface, and that niclosamide has a potential to be developed a novel chemopreventive or therapeutic agent for human prostate and breast cancer.
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“In our previous studies, we have demonstrated that niclosamide (5-chloro-N-[2-chloro-4-nitrophenyl]−2-hydroxy benzamide), an FDA approved antihelminthic drug, suppresses Wnt/β-catenin signaling by promoting Wnt co-receptor LRP6 degradation in cancer cells [27, 37, 38].”
From CI-994 is a dual modulator of class I HDACs and Wnt/β-catenin signaling for the treatment of Alzheimer's disease (2026) · cites this paper as [27]
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“On the other hand, niclosamide can induce Wnt co-receptor LRP6 degradation and suppress Wnt/β-catenin signaling in cancer cells [27, 37, 38], while CI-994 displays the opposite effect on LRP6 regulation by reducing LRP6 turnover.”
From CI-994 is a dual modulator of class I HDACs and Wnt/β-catenin signaling for the treatment of Alzheimer's disease (2026) · cites this paper as [27]
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“On the other hand, niclosamide can induce Wnt co-receptor LRP6 degradation and suppress Wnt/β-catenin signaling in cancer cells [27, 37, 38], while CI-994 displays the opposite effect on LRP6 regulation by reducing LRP6 turnover.”
From CI-994 is a dual modulator of class I HDACs and Wnt/β-catenin signaling for the treatment of Alzheimer's disease (2026) · cites this paper as [27]
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Citations
Cites
Wnt/β-Catenin Signaling: Components, Mechanisms, and Diseases
MacDonald, B. T., Tamai, K., & He, X. (2009) · Developmental Cell · doi:10.1016/j.devcel.2009.06.016 · Cited by 5,583
β-Catenin regulates expression of cyclin D1 in colon carcinoma cells
Tetsu, O., & McCormick, F. (1999) · Nature · doi:10.1038/18884 · Cited by 3,601
Identification of Selective Inhibitors of Cancer Stem Cells by High-Throughput Screening
Gupta, P. B., Önder, T. T., Jiang, G., Tao, K. X., Kuperwasser, C., Weinberg, R. A., & Lander, E. S. (2009) · Cell · doi:10.1016/j.cell.2009.06.034 · Cited by 2,429
The cyclin D1 gene is a target of the β-catenin/LEF-1 pathway
Shtutman, M., Zhurinsky, J., Simcha, I., Albanese, C., D’Amico, M., Pestell, R., & Ben-Ze’ev, A. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.10.5522 · Cited by 2,230
Jho, E., Zhang, T., Domon–Dell, C., Joo, C., Freund, J., & Costantini, F. D. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.4.1172-1183.2002 · Cited by 1,683
Lustig, B., Jerchow, B., Sachs, M., Weiler, S., Pietsch, T., Karsten, U., van de Wetering, M., Clevers, H., Schlag, P., Birchmeier, W., et al. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.4.1184-1193.2002 · Cited by 1,198
LDL-receptor-related proteins in Wnt signal transduction
Tamai, K., Semenov, M., Kato, Y., Spokony, R., Liu, C., Katsuyama, Y., Hess, F., Saint-Jeannet, J.-P., & He, X. (2000) · Nature · doi:10.1038/35035117 · Cited by 1,128
An LDL-receptor-related protein mediates Wnt signalling in mice
Pinson, K. I., Brennan, J., Monkley, S. J., Avery, B. J., & Skarnes, W. C. (2000) · Nature · doi:10.1038/35035124 · Cited by 1,086
Epigenetic inactivation of SFRP genes allows constitutive WNT signaling in colorectal cancer
Suzuki, H., Watkins, D. N., Jair, K.-W., Schuebel, K. E., Markowitz, S. D., Chen, W. D., Pretlow, T. P., Yang, B., Akiyama, Y., van Engeland, M., et al. (2004) · Nature Genetics · doi:10.1038/ng1330 · Cited by 1,074
Targeting cancer stem cells by inhibiting Wnt, Notch, and Hedgehog pathways
Takebe, N., Harris, P. J., Warren, R. Q., & Ivy, S. P. (2010) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2010.196 · Cited by 1,025
Flagged first, then by citations
Cited by
Sorted by citations
Wnt/β-catenin signalling: function, biological mechanisms, and therapeutic opportunities
Liu, J., Xiao, Q., Xiao, J., Niu, C., Li, Y., Zhang, X., Zhou, Z., Shu, G., & Yin, G. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00762-6 · Cited by 2,519
Self-citationWnt/β-catenin signaling in cancers and targeted therapies
Yu, F., Yu, C., Li, F., Zuo, Y., Wang, Y., Yao, L., Wu, C., Wang, C., & Ye, L. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00701-5 · Cited by 734
The Wnt/β-catenin pathway in ovarian cancer: A review
Arend, R. C., Londoño-Joshi, A. I., Straughn, J. M., & Buchsbaum, D. J. (2013) · Gynecologic Oncology · doi:10.1016/j.ygyno.2013.09.034 · Cited by 458
“Our laboratory has seen an increase expression of LRP6 in ovarian cancer patients.”
BackgroundInfluentialNiclosamide: Beyond an antihelminthic drug
Chen, W., Mook, R. A., Premont, R. T., & Wang, J. (2017) · Cellular Signalling · doi:10.1016/j.cellsig.2017.04.001 · Cited by 446
WNT signalling in prostate cancer
Murillo-Garzón, V., & Kypta, R. M. (2017) · Nature Reviews Urology · doi:10.1038/nrurol.2017.144 · Cited by 370
Multi-targeted therapy of cancer by niclosamide: A new application for an old drug
Li, Y., Li, P., Roberts, M. J., Arend, R. C., Samant, R. S., & Buchsbaum, D. J. (2014) · Cancer Letters · doi:10.1016/j.canlet.2014.04.003 · Cited by 367
“Moreover, we recently demonstrated that niclosamide was able to inhibit Wnt/b-catenin signaling by promoting Wnt co-receptor LRP6 degradation, but had no effect on Dvl2 expression in prostate and breast cancer cells [10,11], suggesting that the mechanism underlying niclosamidemediated inhibition of Wnt/b-catenin signa…”
Self-citationDrug repurposing for antimicrobial discovery
Farha, M. A., & Brown, E. D. (2019) · Nature Microbiology · doi:10.1038/s41564-019-0357-1 · Cited by 382
Drug repositioning: a machine-learning approach through data integration
Napolitano, F., Zhao, Y., Moreira, V. M., Tagliaferri, R., Kere, J., D’Amato, M., & Greco, D. (2013) · Journal of Cheminformatics · doi:10.1186/1758-2946-5-30 · Cited by 349
WNT Signaling in Cardiac and Vascular Disease
Foulquier, S., Daskalopoulos, E. P., Lluri, G., Hermans, K. C. M., Deb, A., & Blankesteijn, W. M. (2017) · Pharmacological Reviews · doi:10.1124/pr.117.013896 · Cited by 350
Wnt signaling pathways in biology and disease: mechanisms and therapeutic advances
Chen, X., Chu, Q., Shi, Q., Zeng, Y., Lu, J., & Li, J. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02142-w · Cited by 347
Pez, F., Lopez, A., Kim, M., Wands, J. R., de Fromentel, C. C., & Merle, P. (2013) · Journal of Hepatology · doi:10.1016/j.jhep.2013.07.001 · Cited by 302
“Therapeutic small molecules, such as niclosamide and silibinin, display anti-tumor activity in vitro and in vivo by suppressing Lrp6 expression, leading to inhibition of Wnt/b-catenin signaling in human prostate and breast tumor cells, as well as by promoting induction of apoptosis [114,115].”
BackgroundWnt/β-catenin signalling in prostate cancer
Kypta, R. M., & Waxman, J. (2012) · Nature Reviews Urology · doi:10.1038/nrurol.2012.116 · Cited by 284
Targeting the Wnt pathway in human cancers: Therapeutic targeting with a focus on OMP-54F28
Le, P. N., McDermott, J. D., & Jimeno, A. (2014) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2014.08.005 · Cited by 257
“In this study, Dvl2 was unperturbed, and decreased cell proliferation and apoptosis induction was observed in prostate and breast cancer cells (Lu et al., 2011b).”
BackgroundTranscriptional Regulation of Wnt/β-Catenin Pathway in Colorectal Cancer
Bian, J., Dannappel, M., Wan, C., & Firestein, R. (2020) · Cells · doi:10.3390/cells9092125 · Cited by 261
“LRP Niclosamide [235]; Salinomycin [236]; Monensin [237] Niclosamide (FDA approved) RSPO OMP-131R10 [238] OMP-131R10”
BackgroundYang, K., Wang, X., Zhang, H., Wang, Z., Nan, G., Li, Y., Zhang, F., Mohammed, M. K., Haydon, R. C., Luu, H. H., et al. (2015) · Laboratory Investigation · doi:10.1038/labinvest.2015.144 · Cited by 248
Self-citationWnt/beta-Catenin Signaling and Small Molecule Inhibitors
Voronkov, A. E., & Krauss, S. J. K. (2012) · Current Pharmaceutical Design · doi:10.2174/138161213804581837 · Cited by 227
Li, N., Kaur, P., Bunnag, N., Suresh, J., Sung, I. C. H., Tan, Q. H., Gruber, J., & Tolwinski, N. S. (2019) · Cells · doi:10.3390/cells8080826 · Cited by 228
“Mesd, a specialized chaperone that binds to LRP5/6 on the cell surface, inhibits LRP5/6 ligands and suppresses downstream WNT/β-catenin signaling in prostate cancer [81].”
BackgroundTherapeutic targets of triple‐negative breast cancer: a review
Jamdade, V., Sethi, N., Mundhe, N., Kumar, P., Lahkar, M., & Sinha, N. (2015) · British Journal of Pharmacology · doi:10.1111/bph.13211 · Cited by 210
“Furthermore, the binding of Wnt to its receptors on the cell surface leads to inhibition of the action of this complex (Lu et al., 2011b; King et al., 2012).”
BackgroundInfluentialInhibition of Wnt/β-catenin pathway by niclosamide: A therapeutic target for ovarian cancer
Arend, R. C., Londoño-Joshi, A. I., Samant, R. S., Li, Y., Conner, M., Hidalgo, B., Alvarez, R. D., Landen, C. N., Straughn, J. M., & Buchsbaum, D. J. (2014) · Gynecologic Oncology · doi:10.1016/j.ygyno.2014.04.005 · Cited by 161
Self-citationRepurposing Salicylanilide Anthelmintic Drugs to Combat Drug Resistant Staphylococcus aureus
Rajamuthiah, R., Fuchs, B. B., Conery, A. L., Kim, W., Jayamani, E., Kwon, B., Ausubel, F. M., & Mylonakis, E. E. (2015) · PLoS ONE · doi:10.1371/journal.pone.0124595 · Cited by 148
“Niclosamide was shown to block Wnt signaling in HEK293 cells [61].”
BackgroundResultRecent Development of Wnt Signaling Pathway Inhibitors for Cancer Therapeutics
Harb, J. F., Lin, P.-J., & Hao, J. (2019) · Current Oncology Reports · doi:10.1007/s11912-019-0763-9 · Cited by 139
Drug Screening Identifies Niclosamide as an Inhibitor of Breast Cancer Stem-Like Cells
Wang, Y.-C., Chao, T., Chang, C., Yo, Y.-T., Yu, M.-H., & Lai, H.-C. (2013) · PLoS ONE · doi:10.1371/journal.pone.0074538 · Cited by 128
DiRenzo, D. M., Chaudhary, M. A., Shi, X., Franco, S. R., Zent, J. M., Wang, K., Guo, L., & Kent, K. C. (2016) · Cellular Signalling · doi:10.1016/j.cellsig.2016.02.011 · Cited by 121
“We used Niclosamide, a small molecule inhibitor that abrogates Wnt signaling by promoting Frizzled receptor internalization[20, 21].”
Lü, W., Lin, C., King, T. D., Chen, H., Reynolds, R. C., & Li, Y. (2012) · Cellular Signalling · doi:10.1016/j.cellsig.2012.07.009 · Cited by 122
Self-citationWnt3a: functions and implications in cancer
He, S., Lü, Y., Liu, X., Huang, X., Keller, E. T., Qian, C.-N., & Zhang, J. (2015) · 癌症：英文版 · doi:10.1186/s40880-015-0052-4 · Cited by 119
“Niclosamide and silibinin inhibit LRP6 expression and phosphorylation, block Wnt3a-induced β-catenin accumulation, and inhibit Wnt/β-catenin signaling in HEK293 cells, prostate cancer PC-3 and DU145 cells, and breast cancer MDA-MB-231 and T-47D cells [111, 112].”
BackgroundInfluentialBurock, S., Daum, S., Keilholz, U., Neumann, K., Walther, W., & Stein, U. (2018) · BMC Cancer · doi:10.1186/s12885-018-4197-9 · Cited by 117
“Thus, niclosamide has been reported as an anti-cancer molecule in numerous cancer types like CRC [13], osteosarcoma [42], breast cancer [30, 37], ovarian cancer [31, 43], prostate cancer [44], non-small cell lung cancer (NSCLC) [45, 46], glioblastoma [40], head and neck cancer [47], multiple myeloma, and leukemia [41,…”
Revisiting the role of Wnt/β-catenin signaling in prostate cancer
Schneider, J. A., & Logan, S. K. (2017) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2017.02.008 · Cited by 115
“Salinomycin and Niclosamide, LRP6 antagonists, suppress both cell growth of AR negative PC3 and DU145 cells (Lu and Li, 2014; Lu et al., 2011).”
BackgroundLü, W., & Li, Y. (2014) · Journal of Cellular Biochemistry · doi:10.1002/jcb.24850 · Cited by 109
Self-citationDrug Repositioning for Effective Prostate Cancer Treatment
Turanlı, B., Grøtli, M., Borén, J., Nielsen, J., Uhlén, M., Arğa, K. Y., & Mardinoğlu, A. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.00500 · Cited by 116
“Niclosamide targets the Wnt co-receptor LRP6 on the cell surface and that it is potent molecule as a Wnt/ β -catenin signaling and anti-cancer agent for human prostate and breast cancer due to in vitro studies (Lu et al., 2011).”
Niclosamide repositioning for treating cancer: Challenges and nano-based drug delivery opportunities
Barbosa, E. J., Löbenberg, R., de Araújo, G. L. B., & Bou‐Chacra, N. A. (2019) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2019.05.004 · Cited by 95
Effect of Niclosamide on Basal-like Breast Cancers
Londoño-Joshi, A. I., Arend, R. C., Aristizabal, L., Lu, W., Samant, R. S., Metge, B. J., Hidalgo, B., Grizzle, W. E., Conner, M., Forero-Torres, A., et al. (2014) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-13-0555 · Cited by 97
“Cytosolic free b-catenin analysis was done with GST–Ecadherin binding assay (22).”
BackgroundMethodSelf-citationS100A4 in Cancer Metastasis: Wnt Signaling-Driven Interventions for Metastasis Restriction
Dahlmann, M., Kobelt, D., Walther, W., Mudduluru, G., & Stein, U. (2016) · Cancers · doi:10.3390/cancers8060059 · Cited by 98
“Again, niclosamide reduced levels of LRP6 and β-catenin.”
BackgroundInfluentialAlasadi, A., Chen, M. J., Swapna, G. V. T., Tao, H., Guo, J., Collantes, J. C., Fadhil, N. M., Montelione, G. T., & Jin, S. V. (2018) · Cell Death and Disease · doi:10.1038/s41419-017-0092-6 · Cited by 91
Therapeutic targets in the Wnt signaling pathway: Feasibility of targeting TNIK in colorectal cancer
Masuda, M., Sawa, M., & Yamada, T. (2015) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2015.10.009 · Cited by 96
WNT7A/β-catenin signaling induces FGF1 and influences sensitivity to niclosamide in ovarian cancer
King, M., Lindberg, M. E., Stodden, G. R., Okuda, H., Ebers, S., Johnson, A., MONTAG, A. G., Lengyel, E. R., MacLean, J. A., & Hayashi, K. (2014) · Oncogene · doi:10.1038/onc.2014.277 · Cited by 91
Cevatemre, B., Erkısa, M., Aztopal, N., Karakaş, D., Alper, P., Tsimplouli, C., Sereti, E., DIMAS, K. S., Armutak, E. İ., Gürevin, E. G., et al. (2017) · Pharmacological Research · doi:10.1016/j.phrs.2017.11.027 · Cited by 85
Preclinical evaluation of a nanoformulated antihelminthic, niclosamide, in ovarian cancer
Lin, C.-K., Bai, M.-Y., Hu, T., Wang, Y.-C., Chao, T., Weng, S.-J., Huang, R., Su, P., & Lai, H. (2016) · Oncotarget · doi:10.18632/oncotarget.7113 · Cited by 84
Self-citationLiao, Z., Nan, G., Yan, Z., Zeng, L., Deng, Y., Ye, J., Zhang, Z., Qiao, M., Li, R., Denduluri, S. K., et al. (2015) · Current Cancer Drug Targets · doi:10.2174/1568009615666150629132157 · Cited by 84
“It should also be pointed out that our pathway reporter analysis failed to demonstrate a significant inhibition of the Wnt signal pathway by niclosamide, which is in contrast to several prior reports [36, 37, 41, 46, 47, 53, 54].”
BackgroundResultInfluentialTewari, D., Bawari, S., Sharma, S., DeLiberto, L. K., & Bishayee, A. (2021) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.107876 · Cited by 81
The Roles of Low-Density Lipoprotein Receptor-Related Proteins 5, 6, and 8 in Cancer: A Review
Roslan, Z., Muhamad, M., Selvaratnam, L., & Rahim, S. A. (2019) · Journal of Oncology · doi:10.1155/2019/4536302 · Cited by 80
Targeting Wnt Signaling in Endometrial Cancer
Fatima, I., Barman, S., Rai, R., Thiel, K. W., & Chandra, V. (2021) · Cancers · doi:10.3390/cancers13102351 · Cited by 78
“Niclosamide promoted LRP5/6 degradation [156], Wnt receptor Fzd1 endocytosis [157], downregulation of Dvl2 proteins, and inhibition of Wnt3A-stimulated β-catenin stabilization and TCF/LEF reporter activity [157,158] as well as enhanced cytotoxicity in all the patient derived tumor spheres.”
BackgroundA Role for the WNT Co-Receptor LRP6 in Pathogenesis and Therapy of Epithelial Cancers
Raisch, J., Côté-Biron, A., & Rivard, N. (2019) · Cancers · doi:10.3390/cancers11081162 · Cited by 69
“Moreover, niclosamide, a teniacide of the antihelminthic family, induces LRP6 degradation in breast cancer cell lines, resulting in increased cell apoptosis and decreased cell proliferation (Table 2) [100].”
BackgroundBhushan, B., Dubey, P., Sukumar, U. K., Sachdev, A., Matai, I., & Gopinath, P. (2015) · RSC Advances · doi:10.1039/c4ra15233f · Cited by 71
Mook, R. A., Wang, J., Ren, X.-R., Chen, M., Spasojević, I., Barak, L. S., Lyerly, H. K., & Chen, W. (2015) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2015.07.001 · Cited by 69
Jiang, H., Li, A. M., & Ye, J. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.1004978 · Cited by 69
“Niclosamide-driven Dishevelled-2 and Frizzled 1 degradation may also rely on the induction of autophagosomes (36, 38).”
BackgroundInfluentialMolecules targeting the androgen receptor (AR) signaling axis beyond the AR‐Ligand binding domain
Elshan, N. G. R. D., Rettig, M. B., & Jung, M. E. (2018) · Medicinal Research Reviews · doi:10.1002/med.21548 · Cited by 69
“These results indicate that the LRP6 suppression was not at a transcriptional level but rather mediated by enhanced LRP6 degradation.(80) Niclosamide did not significantly affect the levels of cytosolic disheveled‐2 (Dvl2), another regulator of the Wnt/β‐catenin pathway.”
BackgroundInfluentialInhibition of LEF1-Mediated DCLK1 by Niclosamide Attenuates Colorectal Cancer Stemness
Park, S., Kim, J. Y., Choi, J., Kim, J., Lee, C. J., Singh, P., Sarkar, S., Baek, J., & Nam, J. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-1232 · Cited by 67
“Wnt/b-catenin inhibition by niclosamide has shown anticancer effects including tumor cell growth inhibition and tumor burden reduction in various types of cancer such as colorectal (20, 21), prostate (22), breast cancer (23), and glioblastoma (24).”
BackgroundTremorgenic Mycotoxins: Structure Diversity and Biological Activity
Reddy, P., Guthridge, K. M., Vassiliadis, S., Hemsworth, J. E., Hettiarachchige, I. K., SPANGENBERG, G. C., & Rochfort, S. J. (2019) · Toxins · doi:10.3390/toxins11050302 · Cited by 67
Lü, W., Lin, C., & Li, Y. (2014) · Cellular Signalling · doi:10.1016/j.cellsig.2014.02.018 · Cited by 65
Self-citationWang, Z., Zhao, T., Zhang, S., Wang, J., Chen, Y., Zhao, H., Yang, Y., Shi, S., Chen, Q., & Liu, K. (2021) · Biomarker Research · doi:10.1186/s40364-021-00323-7 · Cited by 63
“For example, niclosamide is an anthelminthic drug used for treating tapeworms in human, whereas accumulating studies also found that it can also target and inhibit the Wnt signaling in multiple types of cancer, such as ovarian cancer [128], colorectal cancer [129], prostate cancer and breast cancer [130], of note is t…”
BackgroundLiu, J., Chen, X., Ward, T. M., Pegram, M. D., & Shen, K. (2016) · Tumor Biology · doi:10.1007/s13277-015-4650-1 · Cited by 63
Jin, B., Wang, C., Li, J., Du, X., Ding, K., & Pan, J. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-0226 · Cited by 63
“Niclosamide lowers the levels of Dishevelled-2 (DVL2) and LRP6, components of the WNT pathway (40, 41).”
BackgroundInfluentialA Second WNT for Old Drugs: Drug Repositioning against WNT-Dependent Cancers
Ahmed, K., Shaw, H., Koval, A., & Katanaev, V. L. (2016) · Cancers · doi:10.3390/cancers8070066 · Cited by 62
“75 μM) [104], suggesting that WNT inhibition is involved in niclosamide’s anticancer effects.”
BackgroundPérez‐Plasencia, C., López–Urrutia, E., García-Castillo, V., Trujano-Camacho, S., López‐Camarillo, C., & Campos-Parra, A. D. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.01037 · Cited by 59
Indole diterpene alkaloids as novel inhibitors of the Wnt/β-catenin pathway in breast cancer cells
Sallam, A. A., Ayoub, N. M., Foudah, A. I., Gissendanner, C. R., Meyer, S. A., & Sayed, K. A. E. (2013) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2013.09.045 · Cited by 59
Chen, L., Wang, L., Shen, H., Lin, H., & Li, D. (2017) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2017.01.140 · Cited by 57
Naqvi, S., Mohiyuddin, S., & Gopinath, P. (2017) · Royal Society Open Science · doi:10.1098/rsos.170611 · Cited by 57
“Studies suggested that anti-proliferative and apoptosis inducing property of niclosamide is due to LRP6 degradation by inhibiting Wnt/b-catenin signalling [14].”
BackgroundNanomedicine to overcome radioresistance in glioblastoma stem-like cells and surviving clones
Séhédic, D., Cikankowitz, A., Hindré, F., Davodeau, F., & Garcion, E. (2015) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2015.02.002 · Cited by 60
Prabhuraj, R. S., Bomb, K., Srivastava, R., & Bandyopadhyaya, R. (2020) · Journal of Polymer Research · doi:10.1007/s10965-020-02092-7 · Cited by 55
The Role of Notch and Wnt Signaling in MSC Communication in Normal and Leukemic Bone Marrow Niche
Kamga, P. T., Bazzoni, R., Collo, G. D., Cassaro, A., Tanasi, I., Russignan, A., Tecchio, C., & Krampera, M. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.599276 · Cited by 57
Yin, L., Gao, Y. L., Zhang, X., Wang, J., Ding, D., Zhang, Y., Zhang, J., & Chen, H. (2016) · Oncotarget · doi:10.18632/oncotarget.9704 · Cited by 54
“Notably, niclosamide inhibited Wnt/β-catenin signaling by enhancing LRP6 degradation in TNBC cells and suppressed TNBC cell proliferation in vitro and tumor growth in vivo [25, 27].”
BackgroundLokhandwala, P. M., Riel, S. L., Haley, L. M., Lu, C., Chen, Y., Silberstein, J. L., Zhu, Y., Zheng, G., Lin, M., Gocke, C. D., et al. (2016) · Journal of Molecular Diagnostics · doi:10.1016/j.jmoldx.2016.08.003 · Cited by 55
Zhang, Y. (2017) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2017.04.086 · Cited by 52
Koval, A., Pieme, C. A., Queiroz, E. F., Ragusa, S., Ahmed, K., Blagodatski, A. S., Wolfender, J., Petrova, T. V., & Katanaev, V. L. (2018) · Cancer Letters · doi:10.1016/j.canlet.2018.08.003 · Cited by 52
Gigantol inhibits Wnt/β-catenin signaling and exhibits anticancer activity in breast cancer cells
Yu, S., Wang, Z., Su, Z., Song, J., Zhou, L., Sun, Q., Liu, S., Li, S., Li, Y., Wang, M., et al. (2018) · BMC Complementary and Alternative Medicine · doi:10.1186/s12906-018-2108-x · Cited by 51
“Multiple small molecule LRP6 inhibitors, such as salinomycin [31], prodigiosin [23], niclosamide [32], silibinin [33] and rottlerin [34], have been identified to exert anticancer activity in breast cancer cells.”
BackgroundSelf-citationZhao, Q., Bi, Y., Zhong, J., Ren, Z., Liu, Y., Jia, J., Yu, M., Tan, Y. L., Zhang, Q., & Yu, X. (2019) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2019.114813 · Cited by 51
Zhao, X., Ma, Y., Luo, J., Xu, K., Tian, P., Lu, C., & Song, J. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e35989 · Cited by 58
“It has been shown to inhibit the WNT/ β -catenin signaling pathway through inducing LRP6 degradation [59].”
BackgroundNiclosamide-conjugated polypeptide nanoparticles inhibit Wnt signaling and colon cancer growth
Bhattacharyya, J., Ren, X.-R., Mook, R. A., Wang, J., Spasojević, I., Premont, R. T., Li, X., Chilkoti, A., & Chen, W. (2017) · Nanoscale · doi:10.1039/c7nr01973d · Cited by 52
Gangrade, A., Pathak, V., Augelli‐Szafran, C. E., Wei, H., Oliver, P. G., Suto, M. J., & Buchsbaum, D. J. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19051524 · Cited by 50
TFAP2 transcription factors are regulators of lipid droplet biogenesis
Scott, C. C., Vossio, S., Rougemont, J., & Grüenberg, J. (2018) · eLife · doi:10.7554/elife.36330 · Cited by 52
“…of the pathway such as Tricostatin A (epigenetic regulator of DKK1 (Vibhakar et al., 2007)) hexachlorophene (ß-catenin inhibitor (Park et al., 2006)), and niclosamide (inducer of LRP6 degradation (Lu et al., 2011)) significantly decreased the appearance of lipid droplets in response to Wnt3a (Fig.”
BackgroundCarotenuto, M., Antonellis, P. D., Liguori, L., Benvenuto, G., Magliulo, D., Alonzi, A., Turino, C., Attanasio, C., Damiani, V., Bello, A. M., et al. (2014) · Oncotarget · doi:10.18632/oncotarget.2169 · Cited by 49
“Here, to exclude further that nuclear translocation of β-catenin is exclusively due to the positive feedback within the cell by Wnt3a, we used niclosamide, which is known to damage Wnt3a/β-catenin signaling activation by inducing LRP6 protein degradation [16].”
BackgroundNiclosamide enhances ROS-mediated cell death through c-Jun activation
Lee, S., Son, A.-R., Ahn, J., & Song, J. (2014) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2014.03.018 · Cited by 49
Cheng, B., Morales, L. D., Zhang, Y., Mito, S., & Tsin, A. T. C. (2017) · PLoS ONE · doi:10.1371/journal.pone.0184324 · Cited by 51
Wnt/β Catenin-Mediated Signaling Commonly Altered in Colorectal Cancer
Deitrick, J., & Pruitt, W. M. (2016) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2016.09.010 · Cited by 48
Wu, N., Zhang, Y., Wang, H.-T., Li, D., Dai, H., Zhang, Q.-Q., Zhang, J., Ma, Y., Xia, Q., Bian, J., et al. (2016) · Cancer Biology & Therapy · doi:10.1080/15384047.2016.1177675 · Cited by 47
“More recently, IWP2, Wnt-C59, sFRP1, sFRP2, sFRP5, Wif1, and DKKs have been reported to inhibit tumors by interfering with the activation of Wnt signaling.(29-34)”
BackgroundWang, L., Xu, M., Fu, L., Chen, X., & Yang, F. (2018) · Scientific Reports · doi:10.1038/s41598-018-30692-3 · Cited by 47
Ahmad, A., Gupta, A., Ansari, M. M., Vyawahare, A., Jayamurugan, G., & Khan, R. (2019) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.9b01947 · Cited by 47
Emergence of Nanotechnology as a Powerful Cavalry against Triple-Negative Breast Cancer (TNBC)
Chaudhuri, A., Kumar, D. N., Dehari, D., Singh, S. P., Kumar, P., Bolla, P. K., Kumar, D. K., & Agrawal, A. K. (2022) · Pharmaceuticals · doi:10.3390/ph15050542 · Cited by 51
“The free β-catenin then translocates from the cytoplasm to the nucleus, where it associates with T-cell factor (TCF)/lymphoid enhancing factor (LEF) to activate the expression of various downstream targeted genes that are responsible for regulating cell growth, proliferation, and apoptosis, thus mediating initiation a…”
BackgroundWinding back Wnt signalling: potential therapeutic targets for treating gastric cancers
Flanagan, D. J., Vincan, E., & Phesse, T. J. (2017) · British Journal of Pharmacology · doi:10.1111/bph.13890 · Cited by 42
Mukherjee, N., & Panda, C. K. (2020) · Clinical Breast Cancer · doi:10.1016/j.clbc.2020.04.004 · Cited by 44
Zeyada, M. S., Abdel‐Rahman, N., El-Karef, A. A., Yahia, S., El-sherbiny, I. M., & Eissa, L. A. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.118458 · Cited by 43
Karakaş, D., Cevatemre, B., Aztopal, N., Arı, F., Yılmaz, V. T., & Ulukaya, E. (2015) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2015.07.026 · Cited by 43
Monin, M. B., Krause, P., Stelling, R., Bocuk, D., Niebert, S., Klemm, F., Pukrop, T., & Koenig, S. (2016) · Journal of Surgical Research · doi:10.1016/j.jss.2016.03.051 · Cited by 42
Deng, Y., Wang, Z., Zhang, F., Qiao, M., Yan, Z., Wei, Q., Wang, J., Liu, H., Fan, J., Zou, Y., et al. (2016) · Cellular Physiology and Biochemistry · doi:10.1159/000447797 · Cited by 40
Zhao, J., He, Q., Gong, Z., Chen, S., & Cui, L. (2016) · SpringerPlus · doi:10.1186/s40064-016-3153-x · Cited by 40
Wnt signalling in gynaecological cancers: A future target for personalised medicine?
Ford, C. E., Henry, C. E., Llamosas, E., Djordjevic, A., & Hacker, N. F. (2015) · Gynecologic Oncology · doi:10.1016/j.ygyno.2015.09.085 · Cited by 39
“number of mechanisms, through inducing LRP5/6 degradation [66], DVL2 down regulation [67, 68], FZD11 endocytosis and inhibits Wnt3a-stimulated β-catenin stabilization[68].”
BackgroundYu, X., Liu, F., Zeng, L., He, F., Zhang, R., Yan, S., Zeng, Z., Shu, Y., Zhao, C., Wu, X., et al. (2018) · Cellular Physiology and Biochemistry · doi:10.1159/000490140 · Cited by 39
Targeting Wnt Signaling for Gastrointestinal Cancer Therapy: Present and Evolving Views
Kim, M. J., Huang, Y., & Park, J. (2020) · Cancers · doi:10.3390/cancers12123638 · Cited by 42
Mudduluru, G., Walther, W., Kobelt, D., Dahlmann, M., Treese, C., Assaraf, Y. G., & Stein, U. (2016) · Drug Resistance Updates · doi:10.1016/j.drup.2016.03.002 · Cited by 37
Kozák, L., Szilágyi, Z., Tóth, L., Pócsi, I., & Molnár, I. (2019) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-018-09594-x · Cited by 38
“These notable activities of penitrem A are due, at least in part, to the inhibition of the Wnt/β-catenin pathway (Sallam et al. 2013a) that is a validated target of novel anticancer drugs (Lu et al. 2011).”
Kauerová, T., Kos, J., Goněc, T., Jampílek, J., & Kollár, P. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17081219 · Cited by 36
Wei, W., Liu, H., Yuan, J., & Yao, Y. (2020) · Fundamental and Clinical Pharmacology · doi:10.1111/fcp.12583 · Cited by 36
Metabolic Strategies for Inhibiting Cancer Development
Icard, P., Loi, M., Wu, Z., Ginguay, A., Lincet, H., Robin, E., Coquerel, A., Berzan, D., Fournel, L., & Alifano, M. (2020) · Advances in Nutrition · doi:10.1093/advances/nmaa174 · Cited by 36
“OXPHOS inhibition Niclosamide (105) Gamatrinib (106) Prostate cancer”
BackgroundJannu, A. K., Puppala, E. R., Gawali, B., Syamprasad, N. P., Alexander, A., Marepally, S. K., Chella, N., Gangasani, J. K., & Naidu, V. G. M. (2021) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2021.120819 · Cited by 36
Niclosamide inhibits lytic replication of Epstein-Barr virus by disrupting mTOR activation
Huang, L., Yang, M., Yuan, Y., Li, X., & Kuang, E. (2016) · Antiviral Research · doi:10.1016/j.antiviral.2016.12.002 · Cited by 36
Combined effects of niclosamide and temozolomide against human glioblastoma tumorspheres
Oh, H.-C., Shim, J., Park, J., Lee, J.-H., Choi, R. J., Kim, N. H., Kim, H. S., Moon, J. H., Kim, E. H., Chang, J. H., et al. (2020) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-020-03330-7 · Cited by 35
“2014), prostate (Lu et al. 2011), lung (Stewart et al.”
BackgroundContribution of the Low-Density Lipoprotein Receptor Family to Breast Cancer Progression
Campion, O., Khalifa, T. A., Langlois, B., Thevenard-Devy, J., Salesse, S., Savary, K., Schneider, C., Etique, N., Dedieu, S., & Devy, J. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.00882 · Cited by 40
“Several drugs such as salinomycin, prodigiosin, and niclosamide indeed induce LRP6 phosphorylation and degradation leading to decreased tumor growth (49, 50, 95).”
BackgroundNiclosamide suppresses macrophage-induced inflammation in endometriosis†
Sekulovski, N., Whorton, A. E., Tanaka, T., Hirota, Y., Shi, M., MacLean, J. A., de Mola, J. R. L., Groesch, K. A., Díaz‐Sylvester, P., Wilson, T. S., et al. (2020) · Biology of Reproduction · doi:10.1093/biolre/ioaa010 · Cited by 33
Fan, X., Xu, J., Files, M. A., Cirillo, J. D., Endsley, J. J., Zhou, J., & Endsley, M. A. (2019) · Tuberculosis · doi:10.1016/j.tube.2019.04.008 · Cited by 33
Niclosamide inhibits ovarian carcinoma growth by interrupting cellular bioenergetics
Shangguan, F., Liu, Y., Ma, L., Qu, G., Lv, Q., An, J., Yang, S., Lü, B., & Cao, Q. (2020) · Journal of Cancer · doi:10.7150/jca.41418 · Cited by 33
Metadata
- Authors
- Lu, W., Lin, C., Roberts, M. J., Waud, W. R., Piazza, G. A., & Li, Y.
- Affiliations
- Southern Research Institute (US)
- University of South Alabama (US)
- Corresponding author
- Li, Yonghe
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2011-12-16
- Volume
- 6
- Issue
- 12
- Pages
- e29290
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3241710
- OpenAlex
- W2007145040
- Cited by
- 230
- References
- 50
- Citations by year
- 2026: 14 · 2025: 13 · 2024: 16 · 2023: 10 · 2022: 12 · 2021: 18 · 2020: 22 · 2019: 19 · 2018: 17 · 2017: 20 · 2016: 21 · 2015: 21 · 2014: 14 · 2013: 8 · 2012: 5
- FWCI
- 3.51
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- University of Rochester
- National Institutes of Health (RO1CA124531)
- National Cancer Institute (R01CA124531)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Hedgehog Signaling Pathway Studies
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- niclosamide, LRP6, Wnt/β-catenin signaling, Wnt co-receptor, protein degradation, prostate cancer, breast cancer, apoptosis, anticancer drug repurposing, antihelminthic drugs, chemoprevention
- MeSH terms
- Dishevelled Proteins, Breast Neoplasms, Drug Screening Assays, Antitumor, Female, Humans, Male, Neoplasm Proteins, Neoplasms, Niclosamide, Phosphoproteins, Phosphorylation, Prostatic Neoplasms, Apoptosis, Cell Line, Tumor, Adaptor Proteins, Signal Transducing, Cell Proliferation, Wnt Proteins, beta Catenin, HEK293 Cells, Proteolysis, Wnt Signaling Pathway, Low Density Lipoprotein Receptor-Related Protein-6, Wnt3A Protein
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