Norcantharidin induces growth inhibition and apoptosis of glioma cells by blocking the Raf/MEK/ERK pathway

World J Surg Oncol. 2014 Jul 15:12:207. doi: 10.1186/1477-7819-12-207.

Abstract

Background: Malignant gliomas represent the most common primary brain tumors. The prognosis of patients with malignant gliomas is poor in spite of current intensive therapy and novel therapeutic modalities are needed. Here we report that norcantharidin is effective in growth inhibition of glioma cell lines in vitro.

Methods: Glioma cell lines (U87 and C6) were treated with norcantharidin. The effects of norcantharidin on the proliferation and apoptosis of glioma cells were measured by 3-[4,5-dimethylthiazol-2-thiazolyl]-2,5-diphenyl-tetrazolium bromide (MTT) assay and flow cytometry. Western blotting was employed to determine the signaling pathway changes.

Results: The results showed that norcantharidin effectively inhibited cell growth and induced apoptosis in glioma cells, which was concurrent with inhibition of the expression of phospho-MEK and phospho-ERK. Furthermore, the expression anti-apoptotic proteins Bcl-2 and Mcl-1 significantly reduced, but no changes in Bcl-xL and Bax.

Conclusions: Our findings demonstrate that norcantharidin is effective for growth inhibition of glioma cell lines and suggest that norcantharidin may be a new therapeutic option for patients with glioma.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Arylamine N-Acetyltransferase / antagonists & inhibitors
  • Blotting, Western
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology*
  • Cell Cycle / drug effects
  • Cell Proliferation / drug effects*
  • Flow Cytometry
  • Glioma / drug therapy
  • Glioma / metabolism
  • Glioma / pathology*
  • Humans
  • MAP Kinase Kinase 1 / antagonists & inhibitors*
  • MAP Kinase Kinase 1 / metabolism
  • Mice
  • Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors*
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors*
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Signal Transduction / drug effects
  • Tumor Cells, Cultured
  • bcl-2-Associated X Protein / metabolism
  • raf Kinases / antagonists & inhibitors*
  • raf Kinases / metabolism

Substances

  • Bridged Bicyclo Compounds, Heterocyclic
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • norcantharidin
  • Arylamine N-Acetyltransferase
  • raf Kinases
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • MAP Kinase Kinase 1
  • MAP2K1 protein, human