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Updated: Mar 25, 2026
A Novel Method: Super-selective Adrenal Venous Sampling
Published on: September 15, 2017
Identification of Niclosamide as a Novel Anticancer Agent for Adrenocortical Carcinoma
Kei Satoh1, Lisa Zhang2, Yaqin Zhang3
1Endocrine Oncology Branch, National Cancer Institute, NIH, Bethesda, Maryland. Icahn School of Medicine at Mount Sinai, New York, New York.
Purpose:
Adrenocortical carcinoma (ACC) is a rare and aggressive cancer, and no current effective therapy is available for locally advanced and metastatic ACC. Drug repurposing is an emerging approach for identifying new indications for existing drugs, especially for rare cancers such as ACC. The objective of this study was to use quantitative high-throughput screening to identify agents with antineoplastic activity against ACC.
Experimental Design:
A screening of 4,292 compounds was performed on three ACC cell lines: BD140A, SW-13, and NCI-H295R.
Results:
Twenty-one active compounds were identified, with an efficacy of >80% in all three cell lines. Of these, niclosamide showed higher efficacy and lower IC50 than established anti-ACC drugs. We then validated niclosamide-inhibited cellular proliferation in all three ACC cell lines. Next, we investigated the mechanism by which niclosamide inhibited ACC cell proliferation, and found that it induced caspase-dependent apoptosis and G1 cell-cycle arrest. Niclosamide also decreased cellular migration and reduced the level of mediators of epithelial-to-mesenchymal transition, such as N-cadherin and vimentin. Furthermore, niclosamide treatment resulted in decreased expression of β-catenin. We also evaluated the effect of niclosamide on energy metabolism in ACC cell lines and found it resulted in mitochondrial uncoupling. Niclosamide treatment inhibited ACC tumor growth with no observed toxicity in mice in vivo
Conclusions:
Our findings suggest that niclosamide has anti-ACC activity through its inhibition of multiple altered cellular pathways and cellular metabolism in ACC. Our results provide a preclinical rationale for evaluating niclosamide therapy in a clinical trial for ACC. Clin Cancer Res; 22(14); 3458-66. ©2016 AACR.
Insights
Niclosamide, an existing drug, shows significant anti-cancer activity against adrenocortical carcinoma (ACC). This study identified niclosamide as a promising agent for ACC treatment, demonstrating efficacy in preclinical models.
Area of Science:
- Oncology
- Pharmacology
- Drug Discovery
Background:
- Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy with limited therapeutic options for advanced stages.
- Drug repurposing offers a viable strategy for identifying novel treatments for rare cancers like ACC.
Purpose of the Study:
- To identify potential anti-cancer agents for ACC through quantitative high-throughput screening.
- To evaluate the efficacy and mechanism of action of identified compounds in ACC models.
Main Methods:
- Screening of 4,292 compounds against three ACC cell lines (BD140A, SW-13, NCI-H295R).
- Validation of lead compounds, including niclosamide, for anti-proliferative effects.
- Investigation of niclosamide's mechanism of action, including apoptosis, cell cycle, epithelial-to-mesenchymal transition (EMT), and cellular metabolism.
- In vivo efficacy and toxicity assessment of niclosamide in mouse models.
Main Results:
- Twenty-one compounds exhibited >80% efficacy across all tested ACC cell lines.
- Niclosamide demonstrated superior efficacy and lower IC50 compared to existing anti-ACC drugs.
- Niclosamide induced apoptosis, G1 cell-cycle arrest, inhibited EMT, and caused mitochondrial uncoupling.
- Niclosamide effectively inhibited ACC tumor growth in vivo with no observed toxicity.
Conclusions:
- Niclosamide exhibits significant anti-ACC activity by targeting multiple cellular pathways and metabolism.
- These findings provide a strong preclinical basis for investigating niclosamide as a therapeutic agent for ACC in clinical trials.
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