Anti-glioma effect of 7-H-pyrrolo [2,3-di]pyrimidine derivative via induction of cell death

Abstract

Purpose: To investigate the effect of 7-H-pyrrolo[2,3-di]pyrimidine derivative (7-HPPD) on glioma cell growth.Methods: Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, while apoptosis was assessed in Hoechst 33342 stained cells using flow cytometry. Changes in cell morphology were assessed by scanning electron microscopy (SEM).Results: Glioma cell viability showed a concentration-dependent decrease on exposure to 7-HPPD for 72 h (p < 0.05). The viabilities of C6, U251 and U87 cells were reduced by 24, 28 and 31 %, respectively, following treatment with 20 μM 7-HPPD. Exposure to various concentrations of 7-HPPDresulted in a marked decrease in BrdU LI and cAMP levels in C6, U251 and U87 glioma cells (p < 0.05). Moreover, 7-HPPD induced apoptosis in U251 and U87 cell cultures, as was evident in the condensation of chromatin material, presence of apoptotic bodies and intense blue fluorescence.Treatment of U251 cells with 7-HPPD for 72 h led to a significant increase in the proportion of cells in G0/G1 phase, and significant decrease in percentage of cells in G2/M and S phases. The population of rounded cells showed a significant rise with increase in 7-HPPD concentration from 10 to 20 μM (p < 0.05).Conclusion: 7-HPPD inhibits growth and proliferation of glioma cells by inducing apoptosis. Therefore, it has a potential for application in glioma chemotherapy. Keywords: Glioma, Fluorescence, Metastasis, Apoptosis, Infiltration