%0 Journal Article
%T Bicyclic triterpenoid Iripallidal induces apoptosis and inhibits Akt/mTOR pathway in glioma cells
%A Nitin Koul
%A Vivek Sharma
%A Deobrat Dixit
%A Sadashib Ghosh
%A Ellora Sen
%J BMC Cancer
%D 2010
%I BioMed Central
%R 10.1186/1471-2407-10-328
%X 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.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.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.Iripallidal [(-) (6R,10S,11S,18R,22S)-26-Hydroxy-22-¦Á-methylcycloirid-16-enal NSC 631939]- a bicyclic triterpenoid isolated from Iris pallida belongs to the terpenoid family as Paclitaxel. Paclitaxel is an effective chemotherapy for several types of neoplasms [1]. Iripallidal inhibited cell growth in a NCI 60 cell line screen [2] and induced cytotoxicity in human tumor cell lines [3]. Besides the fact that Iridals are ligands for phorbol ester receptors with modest selectivity for RasGRP3 [2], not much is known regarding its mechanism of action.Despite recent advances in understanding molecular mechanisms involved in GBM progression, the prognosis of the most malignant brain tumor continues to be dismal. Ras activation occurs in GBMs [4] and this high level of active Ras has been a target for glioma therapy. RasGRP3- is an exchange factor that catalyzes the formation of the active GTP-bound form of Ras-like small GTPases [5]. Importantly, Ras activation stimulates its downstream effector Akt that plays a major role in glioblastoma development as ~80% of GBM cases express high Akt levels
%U http://www.biomedcentral.com/1471-2407/10/328