Imidazo[1,2-a]quinoxaline inhibits proliferation

Malignant gliomas having high incidence and mortality rate are diagnosed as the primary brain tumors worldwide. The present study investigated the effect of imidazo[1,2-a]quinoxaline (IMQ) on LN229 and C6 cell proliferation and evaluated the underlying mechanism. Changes in cell viability were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and apoptosis induction by flow cytometry. Western blotting was used for determination of changes in protein expression. IMQ treatment of LN229 and C6 cells at 5 to 50 μM concentration range significantly (P<0.05) reduced cell viability in dose-dependent manner. Viabilities of LN229 and C6 cells was decreased to 24 and 29%, respectively on treatment with 50 μM IMQ. IMQ treatment of LN229 and C6 cells increased apoptotic cell count to 63.59 and 58.63%, respectively at 50 μM doses. Moreover, IMQ treatment of LN229 and C6 cells led to a significant increase in fraction of the cells in G0/G1 phase. Expression of transforming growth factor beta-1 (TGF-β1) showed a prominent derease in LN229 and C6 cells on treatment with IMQ. Cyclic adenosine 3',5'‑monophosphate, c‑myc, AKT and p‑Ser473‑AKT expression was significantly reduced by IMQ treatment in LN229 and C6 cells. Thus, IMQ exhibits anti-proliferative effect on glioma cell growth via downregulation of TGF-β1 expression and AKT pathway. Therefore, IMQ may be developed as an effective agent for treatment of glioma.