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

The effect of Iripallidal on proliferation and apoptosis on glioma cell lines was evaluated by MTS, colony formation and caspase-3 activity. Akt/mTOR and STAT3 signaling pathways alongwith the molecules associated with cell cycle and DNA damage was evaluated by Western blot analysis. The effect of Iripallidal on telomerase activity and soft agar colony formation was also determined.

Iripallidal induced apoptosis in U87MG, A172, T98G and LN229 glioblastoma cell lines and inhibited Akt/mTOR and STAT3 signaling patway. Alteration of the molecules associated with cell cycle like p21,p27,cyclinD and DNA damage was seen. In addition inhibition of telomerase activity and colony forming efficiency of glioma cells was also seen. Besides Iripallidal also displayed anti-proliferative activity against non-glioma cancer cell lines of diverse origin.

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 glioblastoma multiforme(GBM).

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