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


Jie Wang
Xiang Peng
Chengan Cao
Yan Zhao
Xing Xia

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-HPPD
resulted 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


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eISSN: 1596-9827
print ISSN: 1596-5996