Niclosamide Treatment Suppressed Metastatic, Apoptotic, and Proliferative Characteristics of MDA-MB-231 Cancer Stem...

Area of Science:

• Pharmacology and Toxicology
• Cancer Biology
• Biomedical Engineering

Background:

• Triple-negative breast cancer (TNBC) is characterized by aggressive behavior and high recurrence rates, often driven by cancer stem cells (CSCs).
• Developing effective therapeutic strategies targeting CSCs is crucial for improving treatment outcomes and preventing tumor relapse.

Purpose of the Study:

• To evaluate the efficacy of niclosamide in inhibiting aggressive TNBC CSCs within a 3D bone-mimicking model.
• To investigate the molecular mechanisms underlying niclosamide's action on CSCs, including apoptosis induction and suppression of key oncogenic pathways.

Main Methods:

• Determination of the IC50 dose of niclosamide for inducing apoptosis in MDA-MB-231 CSCs (CD44+/CD24-) using Annexin V/7AAD and WST-1 assays.
• Analysis of protein level changes (p-STAT3, Bax, Bcl-2, Vimentin, ZEB1) via Western Blot.
• Assessment of gene expression alterations (CXCR4, MMP2/9, ABCG1/2, OCT4, NANOG, CCND1, AXIN2, LGR5) using RT-qPCR in a 3D model.

Main Results:

• Niclosamide at 100 μM induced apoptosis in approximately 50% of TNBC CSCs and arrested cells in the G0-G1 phase.
• Treatment significantly suppressed p-STAT3, Bax, Vimentin, ZEB1, and genes associated with metastasis, drug resistance, stemness, and proliferation.
• Niclosamide demonstrated a targeted impact on the CD44+/CD24- CSC population, increasing Bax and decreasing Bcl-2 protein levels.

Conclusions:

• Niclosamide effectively inhibits aggressive TNBC CSCs in a 3D bone-mimicking model by inducing apoptosis and suppressing critical oncogenic pathways.
• The drug's ability to target CSCs and reduce their metastatic and drug-resistant potential suggests it could be a valuable therapeutic agent.
• Niclosamide may enhance CSC sensitivity to conventional treatments, offering a potential strategy to prevent tumor recurrence in TNBC.