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Updated: Jan 20, 2026

Quantitative Measurement of γ-Secretase-mediated Amyloid Precursor Protein and Notch Cleavage in Cell-based Luciferase Reporter Assay Platforms
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γ-Secretase inhibition affects viability, apoptosis, and the stem cell phenotype of endometriotic cells

Laura Ramirez Williams1, Kathrin Brüggemann1, Marina Hubert1

  • 1Department of Gynecology and Obstetrics, Münster University Hospital, Albert-Schweitzer-Campus 1, Münster, Germany.

Acta Obstetricia Et Gynecologica Scandinavica
|August 20, 2019
PubMed
Abstract

Insights

Inhibition of the notch signaling pathway using a gamma-secretase inhibitor (GSI) reduced stemness properties in endometriosis cells. This suggests GSI may be a potential therapeutic strategy for endometriosis treatment.

Area of Science:

  • Endocrinology and Reproductive Biology
  • Cell Biology
  • Molecular Biology

Background:

  • Endometriosis is characterized by aberrant endometrial tissue growth outside the uterus.
  • The notch signaling pathway is implicated in endometriosis pathogenesis due to upregulated receptor expression.
  • Stem cells play a role in the cyclic regeneration of the endometrium, a process potentially affected in endometriosis.

Purpose of the Study:

  • To investigate the effects of notch pathway inhibition on stemness properties of endometriotic cells.
  • To evaluate the therapeutic potential of gamma-secretase inhibitors (GSIs) in endometriosis models.

Main Methods:

  • Treatment of epithelial endometriotic cell line (12Z) and primary endometriotic stroma cells with a GSI.
  • Analysis of gene expression using TaqMan low-density arrays and quantitative PCR.
  • Assessment of functional changes via MTT assay, cell cycle analysis, colony formation, apoptosis assays, and aldehyde dehydrogenase activity assays.
  • Confirmation of protein level changes (LIFR) using flow cytometry.

Main Results:

  • GSI treatment decreased aldehyde dehydrogenase activity and colony formation in 12Z cells.
  • GSI induced G2/M phase arrest, decreased cell viability, and increased apoptosis in both cell models.
  • Transcriptional downregulation of stemness factors (LIFR, SOX2, IFI1, HERP1) was observed.
  • Downregulation of Leukemia Inhibitory Factor Receptor (LIFR) protein was confirmed by flow cytometry.

Conclusions:

  • Gamma-secretase inhibitor (GSI) treatment negatively impacts stemness-associated properties in endometriotic cells.
  • In vitro findings suggest GSI as a potential therapeutic avenue for endometriosis.
  • Further investigation is warranted to explore GSI's efficacy in endometriosis treatment.
Keywords:
Notchendometriosisinterferon-induced transmembrane protein 1leukemia inhibitory factor receptorpodocalyxin-likesex-determining region Y (SRY)- box 2stem cellstherapy

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