JSI-124 inhibits glioblastoma multiforme cell proliferation through G(2)/M cell cycle arrest and apoptosis augment

Cancer Biol Ther. 2008 Aug;7(8):1243-9. doi: 10.4161/cbt.7.8.6263. Epub 2008 Aug 10.

Abstract

JSI-124 (cucurbitacin I) is a selective inhibitor of Janus kinase/signal transducer and activator of transcription 3(JAK/STAT3) and has been shown to exert anti-proliferative and anti-tumor properties both in vitro and in vivo. As STAT3 activation has been implicated in the development of glioma, we investigated the therapeutic efficacy of JSI-124 on glioblastoma multiforme (GBM) by interfering with STAT3 pathway. In present study, two GBM cell lines, U251 and A172 cells, were treated with JSI-124. The results showed that the cell growth was inhibited significantly in a dose-and time-dependent manner. Further investigation illustrated that the levels of phosphorylated-STAT3 were decreased in GBM cells treated by JSI-124, concomitant with apoptosis augment and cell cycle arrest. Specially, JSI-124 induced G(2)/M accumulation via downregulation of cyclin B1 and cdc2 expression. Together these results suggested that inhibition of STAT3 by JSI-124 is a potential strategy for the development of the new glioblastoma multiforme therapeutics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Cell Cycle / genetics*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Dose-Response Relationship, Drug
  • G2 Phase / drug effects
  • Glioblastoma / genetics*
  • Glioblastoma / metabolism
  • Glioblastoma / pathology
  • Humans
  • Mitosis / drug effects
  • Triterpenes / pharmacology*

Substances

  • Antineoplastic Agents
  • Triterpenes
  • cucurbitacin I