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Glabridin inhibits osteosarcoma migration and invasion via blocking the p38- and JNK-mediated CREB-AP1 complexes

Zhiwei Jie1,2, Ziang Xie1,2, Xiangde Zhao1,2

  • 1Department of Orthopaedics, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Journal of Cellular Physiology
|August 28, 2018
PubMed

Insights

Glabridin (GLA), from licorice root, inhibits osteosarcoma growth and metastasis by inducing cell cycle arrest, apoptosis, and reducing invasion. This study reveals GLA

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Osteosarcoma is a prevalent bone cancer impacting children and adolescents.
  • Glabridin (GLA), a licorice root compound, shows antitumor potential but its effect on osteosarcoma is unknown.

Purpose of the Study:

  • To investigate the anti-osteosarcoma and anti-metastatic effects of Glabridin (GLA).
  • To elucidate the underlying molecular mechanisms of GLA's action against osteosarcoma.

Main Methods:

  • In vitro studies using osteosarcoma cell lines (MG63, HOS) and in vivo mouse models.
  • Flow cytometry for cell cycle and apoptosis analysis.
  • Transwell and wound-healing assays for migration and invasion.
  • Western blotting, qRT-PCR, and co-immunoprecipitation for molecular analysis.

Main Results:

  • GLA induced G2/M cell cycle arrest and apoptosis in osteosarcoma cells.
  • GLA significantly reduced osteosarcoma cell migration and invasion.
  • GLA decreased matrix metalloproteinase (MMP)-2 and MMP-9 expression.
  • GLA downregulated p38 MAPK and JNK phosphorylation, and impaired CREB/AP1 complex formation and DNA binding.

Conclusions:

  • Glabridin (GLA) demonstrates significant anti-tumor and anti-metastatic potential in osteosarcoma.
  • GLA acts by disrupting cell cycle progression, promoting apoptosis, and inhibiting key signaling pathways involved in invasion.
  • GLA shows promise as a therapeutic agent for osteosarcoma metastasis prevention and treatment.
Keywords:
CREB-AP1glabridinmetastasisosteosarcomatherapeutic

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