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Published on: October 17, 2025

Niclosamide ethanolamine induces malignant phyllodes tumor cell death via mTOR-TFEB axis-mediated lysosomal

Xinyi He1, Xu Jiang1, Huazhong Lin1

  • 1Department of Pathology, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China.

Journal of Pharmaceutical Sciences
|July 21, 2026
PubMed

Insights

Niclosamide ethanolamine (NEN) inhibits breast malignant phyllodes tumor (MPT) growth by disrupting lysosomal function and inducing apoptosis. This novel mechanism targets the mTOR-TFEB-lysosome axis, offering a potential new treatment for MPT.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Breast malignant phyllodes tumor (MPT) is a recurrent fibroepithelial neoplasm with limited therapeutic options.
  • Surgery is the primary treatment, but recurrence rates remain high.
  • Niclosamide ethanolamine (NEN), an antiparasitic drug, shows potential as a broad-spectrum anticancer agent.

Purpose of the Study:

  • To evaluate the antitumor efficacy of NEN against MPT.
  • To elucidate the molecular mechanisms of NEN's action in MPT.
  • To investigate NEN's impact on autophagy and lysosomal function in MPT cells.

Main Methods:

  • Cell proliferation and migration assays (CCK-8, wound healing, Transwell).
  • Transmission electron microscopy for ultrastructural analysis.
  • Bioinformatics, qPCR, Western blotting, and immunofluorescence to study the mTOR-TFEB-lysosome axis, autophagy, and apoptosis.

Main Results:

  • NEN significantly inhibited MPT cell proliferation and migration.
  • NEN induced autolysosomal accumulation, suppressed mTOR, and promoted TFEB translocation, enhancing lysosomal biogenesis.
  • NEN impaired lysosomal function, leading to autophagic flux blockade, cathepsin leakage, mitochondrial apoptosis, and caspase-3 activation.

Conclusions:

  • NEN kills MPT cells by inducing "lysosomal biogenesis-function uncoupling" via the mTOR-TFEB-lysosome pathway.
  • NEN disrupts lysosomal homeostasis, representing a novel anti-MPT mechanism.
  • NEN is a potential therapeutic candidate for treating malignant phyllodes tumors.
Keywords:
AutophagyBreast phyllodes tumorLysosomeNiclosamide ethanolaminemTOR–TFEB

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