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

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.

• Authors: Nitin Koul, Vivek Sharma, Deobrat Dixit, Sadashib Ghosh, Ellora Sen
• Journal: BMC cancer (BMC Cancer) Vol. 10 Pg. 328 (Jun 24 2010) ISSN: 1471-2407 [Electronic] England
• PMID: 20576128 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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