Related Experiment Video

Updated: Jan 31, 2026

Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay
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Activation of Estrogen Receptor Alpha by Decitabine Inhibits Osteosarcoma Growth and Metastasis

Maria Angeles Lillo Osuna1, Jesus Garcia-Lopez2, Ikbale El Ayachi3

  • 1Department of Orthopaedic Surgery and Biomedical Engineering, University of Tennessee Health Science Center, Memphis, Tennessee.

Cancer Research
|December 30, 2018
PubMed

Insights

Decitabine (DAC) treatment re-induces estrogen receptor alpha (ERα) in osteosarcoma cells, decreasing proliferation and metastasis. This suggests DAC may be a potential therapy for bone cancer by reactivating a tumor suppressor pathway.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Osteosarcoma, a bone malignancy, typically lacks estrogen receptor alpha (ERα) expression due to promoter DNA methylation.
  • Restoring ERα expression could potentially suppress osteosarcoma growth and metastasis.

Purpose of the Study:

  • To investigate the effect of decitabine (DAC), a DNA methylation inhibitor, on ERα expression and osteosarcoma progression.
  • To evaluate the therapeutic potential of DAC in preclinical osteosarcoma models.

Main Methods:

  • Treatment of osteosarcoma cells (143B) with DAC in vitro and in vivo.
  • Analysis of ERα expression, proliferation markers, osteoblast differentiation markers, and metastasis-associated proteins.
  • Overexpression and knockout of ERα using CRISPR/Cas9.
  • Orthotopic mouse models for evaluating tumor growth and metastasis.

Main Results:

  • DAC treatment induced ERα expression, reduced proliferation, and promoted osteoblast differentiation in osteosarcoma cells.
  • DAC decreased metastasis markers (VIMENTIN, SLUG, ZEB1, MMP9) and stem cell markers (SOX2, OCT4, NANOG).
  • ERα overexpression mimicked DAC's effects, while ERα knockout abolished them; DAC inhibited tumor growth and metastasis in vivo.

Conclusions:

  • DNA methylation inhibition by DAC can restore ERα expression, acting as a tumor suppressor in osteosarcoma.
  • DAC demonstrates preclinical efficacy in reducing osteosarcoma proliferation, inducing differentiation, and inhibiting metastasis.
  • DAC shows potential as a repurposed FDA-approved drug for osteosarcoma treatment.

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