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.