The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“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]
The cited source says what the claim attributes to it.
In the citing paper
“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]
The cited source says what the claim attributes to it.
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
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
Items 101–200 of 231
Roos, J., Grösch, S., Werz, O., Schröder, P., Ziegler, S., Fulda, S., Paulus, P., Urbschat, A., Kuhn, B. R., Maucher, I. V., et al. (2015) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2015.11.001 · Cited by 33
Prostate Cancer Stem Cells and Nanotechnology: A Focus on Wnt Signaling
Qin, W., Zheng, Y., Qian, B., & Zhao, M. L. (2017) · Frontiers in Pharmacology · doi:10.3389/fphar.2017.00153 · Cited by 33
Vélez-Vargas, L. C., Santa-González, G. A., Uribe, D., Castañeda, I. C. H., & Pedroza-Díaz, J. (2023) · Pharmaceuticals · doi:10.3390/ph16020276 · Cited by 32
“On the other hand, niclosamide suppressed the LRP6 expression in TNBC MDA-MB-231 cells and ER-positive breast cancer T-47D cells and inhibited breast cancer cell proliferation with IC50 values less than 1 mM [25].”
BackgroundLRP5 regulates the expression of STK40, a new potential target in triple-negative breast cancers
Maubant, S., Tahtouh, T., Brisson, A., Maire, V., Némati, F., Tesson, B. M., Ye, M., Rigaill, G. J., Noizet, M., Dumont, A., et al. (2018) · Oncotarget · doi:10.18632/oncotarget.25187 · Cited by 30
“LRP6 has been identified as a possible treatment target in TNBC [27, 36, 52, 53].”
BackgroundChai, W.-H., Li, Y., Lin, S., Chao, Y.-H., Chen, C.-H., Chan, P.-C., & Lin, C. (2020) · Anticancer Research · doi:10.21873/anticanres.14082 · Cited by 31
Self-citationRen, J., Wang, B., Wu, Q., & Wang, G. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113789 · Cited by 31
Clinical Relevance of Androgen Receptor Splice Variants in Castration-Resistant Prostate Cancer
Maughan, B. L., & Antonarakis, E. S. (2015) · Current Treatment Options in Oncology · doi:10.1007/s11864-015-0375-z · Cited by 29
Drug Repurposing: A New Hope in Drug Discovery for Prostate Cancer
Malik, J. A., Ahmed, S., Momin, S. S., Shaikh, S., Alafnan, A., Alanazi, J., Almermesh, M. H. S., & Anwar, S. (2022) · ACS Omega · doi:10.1021/acsomega.2c05821 · Cited by 31
Liu, J., Chen, X., Ward, T. M., Mao, Y., Bockhorn, J., Liu, X., Wang, G., Pegram, M. D., & Shen, K. (2015) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2015.11.014 · Cited by 29
Endometriotic inflammatory microenvironment induced by macrophages can be targeted by niclosamide†
Sekulovski, N., Whorton, A. E., Shi, M., MacLean, J. A., & Hayashi, K. (2018) · Biology of Reproduction · doi:10.1093/biolre/ioy222 · Cited by 27
Existing drugs and their application in drug discovery targeting cancer stem cells
Lv, J., & Shim, J. S. (2015) · Archives of Pharmacal Research · doi:10.1007/s12272-015-0628-1 · Cited by 29
Zhang, S., Buddenborg, S. K., Adema, C. M., Sullivan, J. T., & Loker, E. S. (2015) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0004131 · Cited by 28
“Recent studies have demonstrated that niclosamide has activity against a variety of cancer cells including those of prostate, breast, ovarian, colon, lung, and head and neck cancers, in part by suppressing various intracellular signaling pathways, including Wnt/beta-catenin, NOTCH, mTORC1, and NF-κB [24, 25].”
BackgroundGao, J., Yu, S., Yuan, Y., Zhang, L., Lu, J., Feng, J., & Hu, S. (2018) · Journal of Cellular Physiology · doi:10.1002/jcp.27056 · Cited by 27
“Suppression of the Wnt–β‐catenin signaling pathway signifies a promising avenue for novel drug development for cancer prevention and treatment (Lu et al., 2011).”
BackgroundRetractedLohiya, G., & Katti, D. S. (2021) · Cancers · doi:10.3390/cancers13133299 · Cited by 27
“Recent studies demonstrate that Niclosamide (Nic), an FDA-approved antihelminthic drug, has shown promising results as a Wnt signaling inhibitor and an anticancer agent [12,13].”
BackgroundWNT signaling in cancer: molecular mechanisms and potential therapies
Liang, J., Pan, Y., Yang, J., Zeng, D., & Li, J. (2025) · Molecular Biomedicine · doi:10.1186/s43556-025-00327-x · Cited by 31
“Currently, niclosamide has demonstrated significant anti-tumor effects in PCa, BC, and CRC [243].”
Niclosamide Analogs for Treatment of Ovarian Cancer
Haygood, C. L. W., Arend, R. C., Gangrade, A., Chettiar, S. N., Regan, N., Hassmann, C. J., Li, P., Hidalgo, B., Straughn, J. M., & Buchsbaum, D. J. (2015) · International Journal of Gynecological Cancer · doi:10.1097/igc.0000000000000506 · Cited by 26
Antihelminthic niclosamide modulates dendritic cells activation and function
Wu, C., Li, Y., Chen, J. J. W., Chen, Y.-C., Chu, C., Pan, I.-H., Wu, Y., & Lin, C. (2014) · Cellular Immunology · doi:10.1016/j.cellimm.2013.12.006 · Cited by 26
Self-citationAkgün, O., Erkısa, M., & Arı, F. (2019) · Journal of Cellular Biochemistry · doi:10.1002/jcb.28813 · Cited by 26
“Previous studies have shown targeting and inhibition of Wnt/β catenin signaling pathway by niclosamide in various tumor types including ovarian,(28) colorectal,(29,30) prostate and breast cancer.(31,32) The anticancer feature is due to a strong STAT3 inhibitor on multiple intracellular signaling pathways,(33) suppress…”
BackgroundMetformin and Niclosamide Synergistically Suppress Wnt and YAP in APC-Mutated Colorectal Cancer
Kang, H. E., Seo, Y., Yun, J. S., Song, S. H., Han, D., Cho, E. S., Cho, S. B., Jeon, Y., Lee, H., Kim, H. S., et al. (2021) · Cancers · doi:10.3390/cancers13143437 · Cited by 25
Li, Z., Yu, Y., Sun, S., Qi, B., WANG, W., & Yu, A. (2015) · Oncology Reports · doi:10.3892/or.2015.3766 · Cited by 25
Rottlerin as a novel chemotherapy agent for adrenocortical carcinoma
Zhu, Y., Wang, M., Zhao, X., Zhang, L., Wu, Y., Wang, B., & Wei-lie, H. (2017) · Oncotarget · doi:10.18632/oncotarget.15221 · Cited by 25
“LRP6 is expressed in human cancer cell lines and up-regulated in human malignant tissues [24], and LRP6 silencing weakens Wnt/β-catenin signaling and inhibits cell proliferation and tumor growth in breast and prostate cancers [25].”
BackgroundSmall molecule modulators of Wnt/β-catenin signaling
Mook, R. A., Chen, M., Lü, J., Barak, L. S., Lyerly, H. K., & Chen, W. (2013) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2013.01.101 · Cited by 24
Liu, Z., Li, Y., Lv, C., Wang, L., & Song, H. (2016) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.08.047 · Cited by 24
Self-citationObianom, O. N., Ai, Y., Li, Y., Yang, W., Guo, D., Yang, H., Sakamuru, S., Xia, M., Xue, F., & Shu, Y. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b01408 · Cited by 24
Self-citationTargeting LRP6: A new strategy for cancer therapy
Xue, W., Zhu, B., Zhao, K., Huang, Q., Luo, H., Shou, Y., Huang, Z., & Guo, H. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107200 · Cited by 22
Kamga, P. T., Collo, G. D., Cassaro, A., Bazzoni, R., Delfino, P., Adamo, A., Bonato, A., Carbone, C., Tanasi, I., Bonifacio, M., et al. (2020) · Cancers · doi:10.3390/cancers12092696 · Cited by 23
“This discrepancy can be explained by the mechanisms triggered by each of the inhibitors; in fact, IWP-2 interferes with biogenesis of Wnt ligand, by targeting porcupine, while Niclosamide interferes directly with the co-receptor LRP-6 [13,42].”
BackgroundMorris, A., Pagare, P. P., Li, J., & Zhang, Y. (2021) · Drug Discovery Today · doi:10.1016/j.drudis.2021.11.014 · Cited by 23
Pharmacological advances and therapeutic applications of niclosamide in cancer and other diseases
Laila, U. E., Zhao, Z., Xu, D., Liu, H., & Xu, Z.-X. (2025) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2025.117527 · Cited by 22
Li, Z., Li, Q., Wang, G., Huang, Y., Mao, X., Zhang, Y., & Wang, X. (2017) · PubMed Central · Cited by 22
Liu, F.-L., Chen, C., Lee, C.-C., Wu, C.-C., Hsu, T.-H., Tsai, C., Huang, H., & Chang, D. (2017) · International Journal of Medical Sciences · doi:10.7150/ijms.19268 · Cited by 21
Salicylanilides and Their Anticancer Properties
Kauerová, T., Pérez‐Pérez, M., & Kollár, P. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24021728 · Cited by 23
Mook, R. A., Ren, X.-R., Wang, J., Piao, H., Barak, L. S., Lyerly, H. K., & Chen, W. (2017) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2017.01.046 · Cited by 21
Mathew, B., Hobrath, J. V., Lü, W., Li, Y., & Reynolds, R. C. (2017) · Medicinal Chemistry Research · doi:10.1007/s00044-017-2001-z · Cited by 20
“The effects of all target compounds on Wnt/β-catenin signaling were examined with the Wnt reporter luciferase assay in HEK293 cells as previously described (Lu et al. 2011; Lu et al. 2012).”
MethodSelf-citationAi, N., Wood, R. D., Yang, E., & Welsh, W. J. (2016) · Pharmaceutical Research · doi:10.1007/s11095-016-2027-9 · Cited by 18
Niclosamide suppresses RANKL-induced osteoclastogenesis and prevents LPS-induced bone loss
Cheon, Y., Kim, J., Baek, J. M., Ahn, S., So, H., & Oh, J. (2016) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.01.048 · Cited by 18
Kauerová, T., Goněc, T., Jampílek, J., Häfner, S., Gaiser, A., Syrovets, T., Fedr, R., Souček, K., & Kollár, P. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21103416 · Cited by 17
Banos, G., Lindsay‐McGee, V., Desta, T. T., Bettridge, J., Sánchez-Molano, E., Vallejo‐Trujillo, A., Matika, O., Dessie, T., Wigley, P., Christley, R., et al. (2020) · Frontiers in Genetics · doi:10.3389/fgene.2020.543890 · Cited by 17
Alqahtani, T., Kumarasamy, V. M., Huczyński, A., & Sun, D. (2019) · International Journal of Oncology · doi:10.3892/ijo.2019.4916 · Cited by 16
“salinomycin, the well‐characterized Wnt inhibitor niclosamide , was used as a positive control in the present study (47,48).”
MethodYi, Y., Woo, Y. M., Hwang, K. H., Kim, H. S., & Lee, S. H. (2021) · Cancers · doi:10.3390/cancers13184630 · Cited by 16
Huang, C., Chen, Y. J., Chen, W. J., Lin, C., Wei, Y., & Huang, H. C. (2014) · Molecular Carcinogenesis · doi:10.1002/mc.22234 · Cited by 16
“reported that silibinin, niclosamide, and rottlerin inhibit breast and prostate cancer cell proliferation by downregulating LRP6 [7,24,25].”
BackgroundSelf-citationLi, Y., Lü, W., Saini, S. K., Moukha‐Chafiq, O., Pathak, V., & Ananthan, S. (2016) · Oncotarget · doi:10.18632/oncotarget.7019 · Cited by 16
“The GST-E-cadherin binding assay was carried out exactly as previously described [32, 33].”
Self-citationStemness regulation in prostate cancer: prostate cancer stem cells and targeted therapy
Liang, H., Zhou, B., Li, P.-X., Zhang, X., Zhang, S., Zhang, Y., Yao, S., Qu, S., & Chen, J. (2024) · Annals of Medicine · doi:10.1080/07853890.2024.2442067 · Cited by 15
Clark-Corrigall, J., Myssina, S., Michaelis, M., Cinatl, J. J., Ahmed, S. U., & Carr‐Wilkinson, J. (2022) · Cancer Investigation · doi:10.1080/07357907.2022.2136682 · Cited by 15
“been reported as an activation molecule for WNT pathway and shown to play a role in carcinogenesis (39,40).”
BackgroundNayak, A., Streiff, H., Adekoya, O. O., Gonzalez, I., Silva, I., & Shenoy, A. K. (2025) · Cells · doi:10.3390/cells14030178 · Cited by 16
“These approaches, combined with thorough preclinical validation and well-structured trial designs, could significantly enhance the success rate of Wnt-targeted therapies in GI cancers, ultimately benefiting patients and paving the way for FDA approval after decades of research and trials.”
Nanoliposomal Encapsulation Enhances In Vivo Anti-Tumor Activity of Niclosamide against Melanoma
Hatamipour, M., Jaafari, M. R., Momtazi‐Borojeni, A. A., Ramezani, M., & Sahebkar, A. (2019) · Anti-Cancer Agents in Medicinal Chemistry · doi:10.2174/1871520619666190705120011 · Cited by 15
Tanaka, T., Asano, T., Okui, T., Kuraoka, S., Singh, S. A., Aikawa, M., & Aïkawa, E. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.826529 · Cited by 14
“Previous studies demonstrated that niclosamide targets several signaling pathways including STAT3 (20, 21), mTORC1 (22), NF-κB and Notch (23, 24), in addition to Wnt (25, 26).”
BackgroundNiclosamide (NA) overcomes cisplatin resistance in human ovarian cancer
Huang, L., Zhang, J., Deng, Y., Wang, H., Zhao, P., Zhao, G., Zeng, W., Wang, Y., Chen, C., Wagstaff, W., et al. (2023) · Genes & Diseases · doi:10.1016/j.gendis.2022.12.005 · Cited by 14
Kang, H. W., Kim, J. H., Da Eun, L. E. E., Lee, Y. S., Kim, M., Kim, H. S., Fang, S., Lee, B., Lee, K. J., Yoo, J., et al. (2023) · Cancer Biology & Therapy · doi:10.1080/15384047.2023.2272334 · Cited by 14
“14 Another study also revealed that niclosamide promotes protein ubiquitination and correlates with poly ADP ribose polymerase (PARP) expression to prove its apoptotic effect in the glioblastoma U-87 MG cell line.”
BackgroundDas, N., Ray, N., PATIL, A. R., Saini, S. S., Waghmode, B., Ghosh, C., Patil, S. B., Patil, S. B., Mote, C., Saini, S. K., et al. (2022) · Food & Function · doi:10.1039/d1fo03727g · Cited by 15
Lin, C., Lü, W., Zhang, W., Londoño-Joshi, A. I., Buchsbaum, D. J., Bu, G., & Li, Y. (2013) · PLoS ONE · doi:10.1371/journal.pone.0058102 · Cited by 14
Self-citationWiggins, R., Woo, J., & Mito, S. (2024) · Cancers · doi:10.3390/cancers16203548 · Cited by 13
“…complex facilitates a series of phosphorylation events along serine–threonine residues; in particular, motifs are found on the β -catenin protein so that it may be tagged for ubiquitination and subsequent proteasomal degradation, effectively downregulating β -catenin target gene transcription [41].”
BackgroundTargeting biologically specific molecules in triple negative breast cancer (TNBC)
Mir, M. A., Sofi, S., & Qayoom, H. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-96136-3.00002-9 · Cited by 13
Identification of DK419, a potent inhibitor of Wnt/β-catenin signaling and colorectal cancer growth
Wang, J., Mook, R. A., Ren, X.-R., Zhang, Q., Jing, G., Lu, M., Spasojević, I., Lyerly, H. K., Hsu, D. S., & Chen, W. (2018) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2018.09.016 · Cited by 13
Combination therapies with Wnt signaling inhibition: A better choice for prostate cancer treatment
Hou, Y., Zhao, Z., Li, P., Cao, Y., Zhang, Y., Guo, C., Nie, X., & Hou, J. (2024) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2024.189186 · Cited by 12
Schumacher, T. J., Iyer, A. V., Rumbley, J. N., Ronayne, C. T., & Mereddy, V. R. (2024) · BMC Cancer · doi:10.1186/s12885-024-13186-6 · Cited by 16
“In the past decade, increasing interest in leveraging niclosamide as an anticancer agent has led to the discovery that niclosamide targets a wide range of pathways such as regulation of Wnt/β-catenin [18, 19], mTORC1 [20–22], STAT3 [23–25], NF-κB [25, 26], and Notch signaling pathways [27, 28].”
Niclosamide’s potential direct targets in ovarian cancer
Sekulovski, N., MacLean, J. A., Bheemireddy, S. R., Yu, Z., Okuda, H., Pru, C. A., Plunkett, K. N., Matzuk, M. M., & Hayashi, K. (2021) · Biology of Reproduction · doi:10.1093/biolre/ioab071 · Cited by 12
Targeting the Wnt signaling pathway for breast cancer bone metastasis therapy
Cui, J., Chen, H., Zhang, K., & Li, X. (2021) · Journal of Molecular Medicine · doi:10.1007/s00109-021-02159-y · Cited by 12
“Niclosamide, an FDA-approved antihelminthic drug, can induce degradation of LRP6 and thereby inhibit the Wnt/βcatenin pathway to induce apoptosis, impair metastasis, and reduce immunosuppression of breast cancer cells [34, 35].”
BackgroundMhatre, O., Reddy, B. P. K., Patnaik, C., Chakrabarty, S., Ingle, A., De, A., & Srivastava, R. (2021) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2021.120278 · Cited by 12
Li, H., Li, J., Zhang, Y., Zhao, C., Ge, J., Sun, Y., Fu, H., & Li, Y. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1401979 · Cited by 12
Self-citationZhang, S., Wang, H., Sai, C., Wang, Y., Cheng, Z., & Zhang, Z. (2025) · Marine Drugs · doi:10.3390/md23050197 · Cited by 11
Resistance mechanisms to epidermal growth factor receptor inhibitors in non-small cell lung cancer
Prabhash, K., Bondili, S. K., Nandhana, R., Noronha, V., Joshi, A., Patil, V., Menon, N. S., Chougule, A., Shetty, O. A., Kumar, R., et al. (2020) · Cancer Research Statistics and Treatment · doi:10.4103/crst.crst_357_20 · Cited by 11
Ngai, T. W., Elfar, G. A., Yeo, P., Phua, N., Hor, J. H., Chen, S., Ho, Y. S., & Cheok, C. F. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221910420 · Cited by 10
Ren, Y., Yu, K., Sun, S., Li, Z., YUAN, J., HAN, X. D., Shi, J.-H., & Zhen, L. (2014) · Oncology Letters · doi:10.3892/ol.2014.2221 · Cited by 11
In Silico Identification of Potential Inhibitors of the Wnt Signaling Pathway in Human Breast Cancer
Pinto, I. A., & da Silveira, N. J. F. (2019) · Journal of Computational Biology · doi:10.1089/cmb.2019.0311 · Cited by 11
“However, as shown by Kuhnert et al. (2004), interrupting the Wnt pathway by blocking interactions to LRP6 results in the loss of gastrointestinal homeostasis in rats, which makes the CRD of the protein FZD7 a more attractive target for the development of treatments.”
LRP6 as a biomarker of poor prognosis of breast cancer
Zhang, Y., Shu, C., Maimaiti, Y., Wang, S., Lu, C., & Zhou, J. (2021) · Gland Surgery · doi:10.21037/gs-21-194 · Cited by 11
“In addition, studies suggest that niclosamide induces LRP6 degradation in breast cancer cell lines, resulting in an increase in tumor cell apoptosis and a decrease in tumor cell proliferation (26).”
BackgroundEvaluation of the Anti-Tumor Activity of Niclosamide Nanoliposomes Against Colon Carcinoma
Hatamipour, M., Jaafari, M. R., Momtazi‐Borojeni, A. A., Ramezani, M., & Sahebkar, A. (2019) · Current Molecular Pharmacology · doi:10.2174/1874467212666190821142721 · Cited by 10
Huo, Y., Chen, W. S., Lee, J., Feng, G., & Newton, I. G. (2019) · Journal of Vascular and Interventional Radiology · doi:10.1016/j.jvir.2019.02.026 · Cited by 10
Li, L., Zhao, L. R., Yang, J., & Zhou, L. (2024) · Medical Oncology · doi:10.1007/s12032-024-02399-1 · Cited by 9
“Niclosamide induces LRP6 degradation by reducing LRP6 expression and phosphorylation, leading to inhibition of cancer cell proliferation, migration, and angiogenesis, as well as apoptosis in various cancers [80–82].”
Mook, R. A., Wang, J., Ren, X.-R., Piao, H., Lyerly, H. K., & Chen, W. (2018) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2018.11.022 · Cited by 9
Progress in triple negative breast carcinoma pathophysiology: Potential therapeutic targets
Yu, K., Rohr, J. M., Liu, Y., Li, M., Xu, J., Wang, K., Chai, J., Zhao, D., Liu, Y., Ma, J., et al. (2020) · Pathology - Research and Practice · doi:10.1016/j.prp.2020.152874 · Cited by 9
Drug Repositioning Strategies to Explore New Candidates Treating Prostate Cancer
Turanlı, B., & Arğa, K. Y. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-816125-8.00027-4 · Cited by 9
The Relationship between LRP6 and Wnt/β-Catenin Pathway in Colorectal and Esophageal Cancer
Shishido, A., Miyo, M., Oishi, K., Nishiyama, N., Wu, M., Yamamoto, H., Kouda, S., Wu, X., Shibata, S., Yokoyama, Y., et al. (2023) · Life · doi:10.3390/life13030615 · Cited by 11
“With regards to LRP6, Niclosamide [45], Salinomycin [46], and Rottlerin [47] are known to suppress LRP6 expression.”
BackgroundKang, M., Kim, M. J., Kim, A., Koo, T., Lee, K., & Chae, Y. (2024) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2024.110886 · Cited by 10
Double Repositioning: Veterinary Antiparasitic to Human Anticancer
Sultana, T., Jan, U., & Lee, J. I. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23084315 · Cited by 9
Li, Y., Oliver, P. G., Lü, W., Pathak, V., Sridharan, S., Augelli‐Szafran, C. E., Buchsbaum, D. J., & Suto, M. J. (2016) · Cancer Letters · doi:10.1016/j.canlet.2016.12.030 · Cited by 7
Self-citationRetractedBerenguier, C., Chen, X., Allegrini, B., Guizouarn, H., Borgèse, F., Etchebest, C., Soriani, O., & Rapetti‐Mauss, R. (2025) · Oncogene · doi:10.1038/s41388-025-03447-4 · Cited by 7
“Cells expressing WT or LOF-mutated KCNQ1 were treated with niclosamide (5 μ M), a Frizzled inhibitor, which reduced Frizzled membrane density [43].”
Park, J., Yoo, H.-J., Yu, A.-R., Kim, H. O., Park, S. C., Jang, Y. P., Lee, C., Choe, W., Kim, S. S., Kang, I., et al. (2021) · Journal of Microbiology and Biotechnology · doi:10.4014/jmb.2012.12015 · Cited by 7
“Phosphorylated β-catenin is multi-ubiquitinated by E3 ubiquitin ligase β-transducin repeatcontaining protein (β-TrCP) and degraded by the 26S proteasome [9].”
BackgroundSyamprasad, N. P., Madje, N., Bachannagari, J., Jannu, A. K., Jain, S., Tene, K., Shantanu, P. A., Naidu, V. G. M., & Chella, N. (2023) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2023.104221 · Cited by 7
The Importance of Cancer Stem Cells and Their Pathways in Endometrial Cancer: A Narrative Review
Caravia, L. G., Mitranovici, M.-I., Oală, I. E., Tiron, A. T., SIMIONESCU, A. A., Borcan, A. M., & Craina, M. L. (2025) · Cells · doi:10.3390/cells14080594 · Cited by 7
“Niclosamide, which is used in the treatment of tape-worm infections, targets the Wnt/ β -catenin pathway [96–98].”
Jeengar, M. K., Kumar, S., Shrivastava, S., Syamprasad, N. P., Katanaev, V. L., Uppugunduri, S., & Naidu, V. G. M. (2020) · Asia-Pacific Journal of Oncology · doi:10.32948/ajo.2020.08.06 · Cited by 6
Romo‐Pérez, A., Domínguez-Gómez, G., Chávez-Blanco, A. D., González‐Fierro, A., Correa‐Basurto, J., & Dueñas‐González, A. (2023) · Current Medicinal Chemistry · doi:10.2174/0929867330666230607104441 · Cited by 6
Waye, A. A., Ticiani, E., Sharmin, Z., Pérez‐Silos, V., Perera, T., Tu, A., Buhimschi, I. A., Murga‐Zamalloa, C., Hu, Y., & Veiga‐Lopez, A. (2024) · Chemosphere · doi:10.1016/j.chemosphere.2024.143301 · Cited by 5
Sun, M., Zhu, H., Yu, Y., Yao, Y., Li, H.-Y., Feng, F., Wang, Q., Liu, R.-J., & Sun, C.-G. (2025) · International Journal of Oncology · doi:10.3892/ijo.2025.5742 · Cited by 8
“In BC cell models, niclosamide inhibits cellular proliferation and promotes apoptosis without affecting DVL2 expression (213,214).”
Koval, A., Boudou, C., & Katanaev, V. L. (2024) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.4c00570 · Cited by 5
Lu, W., Kawatani, K., Ren, Y., Nambara, T., Jia, L., Jeevaratnam, S., Lee, E., Martinez, P. R., Izhar, T., Wang, N., et al. (2026) · Alzheimer's Research & Therapy · doi:10.1186/s13195-026-01982-0 · Cited by 4
Self-citationSoltani, Z. E., Elahi, M. M., Rad, M. A., Farsio, S., & Dehpour, A. R. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e33050 · Cited by 4
“Recent studies have shown niclosamide could be used as a treatment for cancers [20 – 23], bacterial infections [24,25], viral infections [26,27], and type-2 diabetes [28].”
BackgroundBellis, C., Mlaza, M., Ali, A. S., Abrahams, A., & Prince, S. (2025) · Biochemical Society Transactions · doi:10.1042/bst20241069 · Cited by 3
Pharmacological interventions part III
Koltai, T., Reshkin, S. J., & Harguindey, S. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-819059-3.00015-0 · Cited by 4
Lam, S. K., Yan, S., Lam, J. S.-M., Feng, Y., Khan, M., Chen, C., Ko, F. C. F., & Ho, J. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.1020343 · Cited by 4
“, 2016), prostate (Lu et al., 2011) and renal (Yu et al.”
BackgroundTargeting the Key Signaling Pathways in Breast Cancer Treatment Using Natural Agents
Anandasadagopan, S. K., Sivaprakasam, P., Pathmanapan, S., Pandurangan, A. K., & Alagumuthu, T. (2020) · Springer eBooks · doi:10.1007/978-981-15-2361-8_7 · Cited by 4
Pathak, V., Augelli‐Szafran, C. E., Wei, H., Li, Y., Oliver, P. G., Lü, W., Buchsbaum, D. J., & Suto, M. J. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b01417 · Cited by 4
Self-citationRetractedA High‐Throughput Drug Repurposing Strategy to Treat TBX2 and/or TBX3 Dependent Cancers
Bleloch, J., Lu, S., Khan, S. F., Serala, K., Seraia, E., Millar, V., Ebner, D. V., Goding, C. R., & Prince, S. (2024) · Cancer Medicine · doi:10.1002/cam4.70303 · Cited by 3
“In vitro studies have explored niclosamide for the treatment of several cancers including breast, colon, ovarian, prostate, lung, glioblastoma and osteosarcoma where it can inhibit cell migration, invasion, proliferation and induce apoptosis [36–42].”
BackgroundS100A4 (S100 calcium binding protein A4)
Sherbet, G. V. (2012) · Atlas of Genetics and Cytogenetics in Oncology and Haematology · doi:10.4267/2042/46036 · Cited by 3
Drug repurposing in oncology: Bridging computational discovery to clinical application
Baskar, S., & Prasad, N. R. (2026) · International Journal of Cancer · doi:10.1002/ijc.70429 · Cited by 2
Beyond the target: implications of Wnt pathway inhibitors on bone health
Nachef, C., Vanjak, A., Haÿ, E., Cohen-Solal, M. E., & Funck‐Brentano, T. (2026) · Journal of Molecular Medicine · doi:10.1007/s00109-026-02697-3 · Cited by 2
“Niclosamide, originally an anti-helminthic, has recently been discovered to inhibit the Wnt pathway by targeting LRP6 [53].”
Therapeutic Effect of Niclosamide versus Triamcinolone on Rabbit Ear Model of Hypertrophic Scar
Ghazy, D. N., Abu-Raghif, A. R., Almansoori, A. O. T., Al-Asady, F. M., Al-Saray, D. A., Abed, D. A., Abbas, S. N., & Salman, H. (2026) · Aesthetic Plastic Surgery · doi:10.1007/s00266-026-06104-7 · Cited by 2
“It primarily targets the Wnt/β-catenin pathway, which promotes fibroblast growth, myofibroblast formation, and overproduction of ECM constituents like collagen types I and III [42, 124, 125].”
An Insight on Colon Cancer Stem Cells and Its Therapeutic Implications
Pournami Gopan, S., Das, A., Esmeeta, A., Deka, D., Duttaroy, A. K., Pathak, S., & Banerjee, A. (2023) · Springer eBooks · doi:10.1007/978-981-99-2196-6_63-1 · Cited by 2
Niclosamide is a potential candidate for the treatment of chemo-resistant osteosarcoma
Huang, X., Wang, W., & Li, Y. (2023) · Genetics and Molecular Biology · doi:10.1590/1678-4685-gmb-2022-0136 · Cited by 2
“…that niclosamide induces apoptosis and cell cycle arrest for numerous cancers that include ovary, intestinal, liver, cervix, kidney, breast and blood (Khanim et al., 2011; Lu et al., 2011; Osada et al., 2011; Arend et al., 2014; Zhao et al., 2016; Chen et al., 2017; Wang C et al., 2018).”
Self-citationFaheem, S. A., Hazem, R. M., El-Sayed, N. M., Ahmed, Y. M., & Saeed, N. M. (2023) · International Immunopharmacology · doi:10.1016/j.intimp.2023.109941 · Cited by 2
Myssina, S., Clark-Corrigall, J., Michaelis, M., Cinatl, J. J., Ahmed, S. U., & Carr‐Wilkinson, J. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/449785 · Cited by 2
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
