SP600125, a JNK inhibitor, suppresses growth of JNK-inactive glioblastoma cells through cell-cycle G2/M phase arrest

Pharmazie. 2012 Nov;67(11):942-6.

Abstract

SP600125 is a well studied inhibitor of c-Jun N-terminal kinase (JNK). Its direct biochemical effects on JNK-inactive tumor cells are usually ignored. In this study, we investigated the effects of SP600125 on JNK-inactive U251 human glioblastoma cells. Our results demonstrate that, 20 microM or more SP600125 can induce significant cell growth inhibition and cell-cycle G2/M phase arrest in U251 cells. Interestingly, we also found that SP600125 can stop the duplicated chromosomes from separating into two cells and the karyokinesis progression. Our study opened up a new perspective for further studies involved in JNK inhibitors or anti-glioma therapy.

MeSH terms

  • Anthracenes / pharmacology*
  • Benzimidazoles
  • Blotting, Western
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / enzymology
  • Brain Neoplasms / pathology
  • CDC2 Protein Kinase / metabolism
  • Cell Line, Tumor
  • Cell Nucleus / drug effects
  • Cell Nucleus / ultrastructure
  • Enzyme Inhibitors / pharmacology*
  • Flow Cytometry
  • Fluorescent Dyes
  • G2 Phase Cell Cycle Checkpoints / drug effects*
  • Glioblastoma / drug therapy*
  • Glioblastoma / enzymology
  • Glioblastoma / pathology
  • Humans
  • M Phase Cell Cycle Checkpoints / drug effects*
  • MAP Kinase Kinase 4 / antagonists & inhibitors*
  • Vacuoles / drug effects
  • Vacuoles / ultrastructure

Substances

  • Anthracenes
  • Benzimidazoles
  • Enzyme Inhibitors
  • Fluorescent Dyes
  • pyrazolanthrone
  • CDC2 Protein Kinase
  • MAP Kinase Kinase 4
  • bisbenzimide ethoxide trihydrochloride