Naringin suppresses the development of glioblastoma by inhibiting FAK activity

J Drug Target. 2017 Jan;25(1):41-48. doi: 10.1080/1061186X.2016.1184668. Epub 2016 May 18.

Abstract

As the most common and lethal primary malignant brain cancer, glioblastoma is hard to timely diagnose and sensitive therapeutic monitoring. It is essential to develop new and effective drugs for glioblastoma multiform. Naringin belongs to citrus flavonoids and was found to display strong anti-inflammatory, antioxidant and antitumor activities. In this report, we found that naringin can specifically inhibit the kinase activity of FAK and suppress the FAKp-Try397and its downstream pathway in glioblastoma cells. Our study showed out that naringin can inhibit cell proliferation by inhibiting FAK/cyclin D1 pathway, promote cell apoptosis through influencing FAK/bads pathway, at the same time, it can also inhibit cell invasion and metastasis by inhibiting the FAK/mmps pathway. All these showed that naringin exerts the anti-tumor effects in U87 MG by inhibiting the kinase activity of FAK.

Keywords: FAK; glioblastoma; metastasis; naringin; proliferation.

MeSH terms

  • Apoptosis / drug effects
  • Brain Neoplasms / enzymology
  • Brain Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Flavanones / chemistry
  • Flavanones / pharmacology*
  • Focal Adhesion Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Glioblastoma / enzymology
  • Glioblastoma / pathology*
  • Humans
  • Molecular Structure
  • Phosphorylation
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*

Substances

  • Flavanones
  • Protein Kinase Inhibitors
  • Focal Adhesion Protein-Tyrosine Kinases
  • naringin