Inhibition of Wnt/β-catenin pathway by niclosamide: A therapeutic target for ovarian cancer
Abstract
Objective. The Wnt/β-catenin pathway is known to regulate cellular proliferation and plays a role in chemoresistance. Niclosamide, an FDA approved salicyclamide derivative used for the treatment of tapeworm infections, targets the Wnt/β-catenin pathway. Therefore, the objective of this study was to investigate niclosamide as a potential therapeutic agent for ovarian cancer. Methods. Tumor cells isolated from 34 patients' ascites with primary ovarian cancer were treated with niclosamide (0.1 to 5 μM) ± carboplatin (5 to 150 μM). Cell viability was assessed using the ATP-lite assay. LRP6, Axin 2, Cyclin D1, survivin and cytosolic free β-catenin levels were determined using Western blot analysis. Tumorspheres were treated, and Wnt transcriptional activity was measured by the TOPflash reporter assay. ALDH and CD133 were analyzed by Flow cytometry and IHC. ALDH1A1 and LRP6 were analyzed by IHC in solid tumor and in ascites before and after treatment with niclosamide. Results. Combination treatment produced increased cytotoxicity compared to single agent treatment in 32/34 patient samples. Western blot analysis showed a decrease in Wnt/β-catenin pathway proteins and the expression of target genes. A significant reduction of Wnt/β-catenin signaling was confirmed by TOPflash assay. There was increased staining of ALDH1A1 and LRP6 in ascites compared to solid tumor which decreased after treatment. Conclusion. This study demonstrates that niclosamide is a potent Wnt/β-catenin inhibitor…
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Niclosamide suppresses Wnt/β-catenin signaling by promoting Wnt co-receptor LRP6 degradation in cancer cells.
“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 [38]
Niclosamide suppresses Wnt/β-catenin signaling in cancer cells.
“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 [38]
Niclosamide induces Wnt co-receptor LRP6 degradation in cancer cells.
“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 [38]
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Wnt/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 · see citing works
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LGR5 is associated with tumor aggressiveness in papillary thyroid cancer
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- Authors
- 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.
- Affiliations
- University of Alabama at Birmingham (US)
- Corresponding author
- Arend, Rebecca C.
- ORCID
- Venue
- Gynecologic Oncology
- Publisher
- Elsevier BV
- Published
- 2014-07
- Volume
- 134
- Issue
- 1
- Pages
- 112-120
- ISSN
- 0090-8258 (ISSN-L)
- OpenAlex
- W2006054934
- Cited by
- 161
- References
- 2
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 7 · 2023: 9 · 2022: 18 · 2021: 14 · 2020: 12 · 2019: 9 · 2018: 16 · 2017: 17 · 2016: 19 · 2015: 27 · 2014: 3
- FWCI
- 9.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Gynecologic Oncology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Alabama at Birmingham
- China Scholarship Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Reproductive Medicine › Ovarian cancer diagnosis and treatment
- Keywords
- niclosamide, Wnt/β-catenin signaling, ovarian cancer, LRP6, chemoresistance, ALDH1A1, cancer stem cells, ascites, drug repurposing, cell proliferation inhibition
- MeSH terms
- AC133 Antigen, Aldehyde Dehydrogenase, Antineoplastic Combined Chemotherapy Protocols, Ascites, Dose-Response Relationship, Drug, Drug Screening Assays, Antitumor, Female, Glycoproteins, Humans, Niclosamide, Ovarian Neoplasms, Peptides, Neoplastic Stem Cells, Antigens, CD, Carboplatin, Cell Line, Tumor, Wnt Signaling Pathway
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