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Cited by 97Wnt/β-catenin signaling in development and cancerCancer Cells and MetastasisBreast Cancer Treatment Studies

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Effect of Niclosamide on Basal-like Breast Cancers

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Londoño-Joshi, Angelina I., Arend, Rebecca C., Aristizabal, Laura, Lu, Wenyan, Samant, Rajeev S., Metge, Brandon J., Hidalgo, Bertha, Grizzle, William E., Conner, Michael, Forero-Torres, Andres, LoBuglio, Albert F., Li, Yonghe, Buchsbaum, Donald J.·2014·Molecular Cancer Therapeutics
DOI 10.1158/1535-7163.mct-13-0555PMC PMC3981919

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Abstract

Basal-like breast cancers (BLBC) are poorly differentiated and display aggressive clinical behavior. These tumors become resistant to cytotoxic agents, and tumor relapse has been attributed to the presence of cancer stem cells (CSC). One of the pathways involved in CSC regulation is the Wnt/β-catenin signaling pathway. LRP6, a Wnt ligand receptor, is one of the critical elements of this pathway and could potentially be an excellent therapeutic target. Niclosamide has been shown to inhibit the Wnt/β-catenin signaling pathway by causing degradation of LRP6. TRA-8, a monoclonal antibody specific to TRAIL death receptor 5, is cytotoxic to BLBC cell lines and their CSC-enriched populations. The goal of this study was to examine whether niclosamide is cytotoxic to BLBCs, specifically the CSC population, and if in combination with TRA-8 could produce increased cytotoxicity. Aldehyde dehydrogenase (ALDH) is a known marker of CSCs. By testing BLBC cells for ALDH expression by flow cytometry, we were able to isolate a nonadherent population of cells that have high ALDH expression. Niclosamide showed cytotoxicity against these nonadherent ALDH-expressing cells in addition to adherent cells from four BLBC cell lines: 2LMP, SUM159, HCC1187, and HCC1143. Niclosamide treatment produced reduced levels of LRP6 and β-catenin, which is a downstream Wnt/β-catenin signaling protein. The combination of TRA-8 and niclosamide produced additive cytotoxicity and a reduction in Wnt/β-catenin activity. Niclosamide in combination with TRA-8 suppressed growth of 2LMP orthotopic tumor xenografts. These results suggest that niclosamide or congeners of this agent may be useful for the treatment of BLBC. Mol Cancer Ther; 13(4); 800–11. ©2014 AACR.

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Metadata

Authors
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., LoBuglio, A. F., Li, Y., & Buchsbaum, D. J.
Affiliations
  • Southern Research Institute (US)
  • Authors' Affiliations: Departments of 1Pathology, 2Biology, 3Biostatistics, 4Medicine, and 5Radiation Oncology; 6Division of Gynecologic Oncology; 7Southern Research Institute; and 8Division of Hematology and Onocology, University of Alabama at Birmingham, Birmingham, Alabama
Corresponding author
  • Londoño-Joshi, Angelina I.
  • Buchsbaum, Donald J.
ORCID
Venue
Molecular Cancer Therapeutics
Publisher
American Association for Cancer Research (AACR)
Published
2014-04-01
Volume
13
Issue
4
Pages
800-811
ISSN
  • 1535-7163 (ISSN-L)
  • 1538-8514
DOI
10.1158/1535-7163.mct-13-0555
PMC
PMC3981919
OpenAlex
W2051456050
Cited by
97
References
1
Citations by year
2026: 3 · 2025: 5 · 2024: 5 · 2023: 6 · 2022: 8 · 2021: 5 · 2020: 11 · 2019: 7 · 2018: 14 · 2017: 4 · 2016: 16 · 2015: 9 · 2014: 4
FWCI
4.51
Type
journal article
Language
en
Open access
Locations
  • Molecular Cancer Therapeutics (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • University of Miami
  • China Scholarship Council
  • Agence Nationale pour la Gestion des Déchets Radioactifs
  • National Institutes of Health
  • U.S. Food and Drug Administration
  • National Heart, Lung, and Blood Institute (T32HL072757)
  • National Cancer Institute (R01CA124531, T32CA091078, P50CA089019, P30CA013148)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR 48311, P30AR048311)
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
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
Keywords
niclosamide, basal-like breast cancer, cancer stem cells, Wnt/β-catenin signaling, LRP6, TRA-8, aldehyde dehydrogenase, combination therapy, orthotopic xenograft, cytotoxicity
MeSH terms
Animals, Antibodies, Monoclonal, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Breast Neoplasms, Female, Humans, Mammary Neoplasms, Experimental, Mice, Nude, Niclosamide, Neoplastic Stem Cells, Gene Expression Regulation, Neoplastic, Neoplasms, Basal Cell, Xenograft Model Antitumor Assays, Cell Line, Tumor, Mice, Wnt Signaling Pathway

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