Bicyclic triterpenoid Iripallidal induces apoptosis and inhibits Akt/mTOR pathway in glioma cells

BMC Cancer. 2010 Jun 24;10:328. doi: 10.1186/1471-2407-10-328.

Abstract

Background: The highly resistant nature of glioblastoma multiforme (GBM) to chemotherapy prompted us to evaluate the efficacy of bicyclic triterpenoid Iripallidal against GBM in vitro.

Methods: The effect of Iripallidal on proliferation and apoptosis in glioma cell lines was evaluated by MTS, colony formation and caspase-3 activity. The effect of iripallidal to regulate (i) Akt/mTOR and STAT3 signaling (ii) molecules associated with cell cycle and DNA damage was evaluated by Western blot analysis. The effect of Iripallidal on telomerase activity was also determined.

Results: Iripallidal (i) induced apoptosis, (ii) inhibited Akt/mTOR and STAT3 signaling, (iii) altered molecules associated with cell cycle and DNA damage, (iv) inhibited telomerase activity and colony forming efficiency of glioma cells. In addition, Iripallidal displayed anti-proliferative activity against non-glioma cancer cell lines of diverse origin.

Conclusion: The ability of Iripallidal to serve as a dual-inhibitor of Akt/mTOR and STAT3 signaling warrants further investigation into its role as a therapeutic strategy against GBM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrolein / analogs & derivatives*
  • Acrolein / pharmacology
  • Apoptosis / drug effects*
  • Blotting, Western
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Caspase 3 / metabolism
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cyclohexanols / pharmacology*
  • Glioblastoma / drug therapy*
  • Glioblastoma / metabolism
  • Glioblastoma / pathology
  • Humans
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • TOR Serine-Threonine Kinases / metabolism*
  • Telomerase / antagonists & inhibitors
  • Telomerase / metabolism

Substances

  • 26-hydroxy-22-methylcycloirid-16-enal
  • Cyclohexanols
  • Acrolein
  • TOR Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Telomerase
  • Caspase 3