Cholesterol-Lowering Treatment Blocks Epithelial-Mesenchymal Transition (EMT) Associated Invasiveness and Drug

Shanen Perumal1, Naaziyah Abdulla1, Ruth Aronson1

  • 1School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, South Africa.

Cancer Medicine
|July 1, 2026
PubMed
Abstract

Insights

Cholesterol depletion reversed cancer cell changes associated with metastasis and drug resistance. This suggests lowering cholesterol could be a new strategy to fight cancer progression.

Area of Science:

  • Cell Biology
  • Cancer Research
  • Biochemistry

Background:

  • Epithelial-mesenchymal transition (EMT) drives cancer cell invasion and metastasis.
  • Altered cholesterol metabolism is linked to cancer treatment resistance and metastasis.
  • The relationship between EMT and cellular cholesterol levels remains unclear.

Purpose of the Study:

  • To investigate the effect of cholesterol-lowering interventions on EMT.
  • To determine if modulating cholesterol impacts cancer cell metastatic potential and drug resistance.

Main Methods:

  • Utilized three cancer cell lines (NMuMG, MCF-7, HT-29) and three EMT inducers.
  • Administered cholesterol-modulating compounds (MβCD, HPβCD, simvastatin).
  • Assessed changes in free cholesterol, lipid droplets, lipid rafts, and EMT-associated gene expression via immunofluorescence, RT-qPCR, and Western blotting.

Main Results:

  • Cholesterol depletion using HPβCD reversed EMT markers, increasing CDH1 and decreasing Vim expression in NMuMG cells.
  • Reduced expression of cholesterol biosynthesis (HMGCR) and efflux (ABCA1, ABCG1) genes was observed.
  • Significant reductions in NMuMG cell invasion (68.4%) and MCF-7 cell multidrug resistance (41.3%) were noted post-treatment.

Conclusions:

  • Cholesterol depletion effectively reversed EMT-associated molecular alterations across multiple cell models.
  • These findings highlight cholesterol depletion as a promising therapeutic approach to combat metastatic cancer progression and enhance treatment efficacy.

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