Neovibsanin B inhibits human malignant brain tumor cell line proliferation and induces apoptosis.

The present study was designed to examine the effect of neovibsanin B on glioma cell viability, apoptosis and on the survival time in mice bearing tumor xenografts. The results demonstrated that neovibsanin B significantly reduced the cell viability of GL261-NS and GL261-AC cells in a dose-dependent manner. However the inhibition of proliferation was more significant in GL261-NS cells. The IC50 value of neovibsanin B against GL261-NS and GL261-AC cells is 5 and 25 nM, respectively. The inhibitory effect of neovibsanin B on cell growth was more effective than that of vincristine (VCR) (P < 0.05). We also observed a significant decrease in sphere-forming ability of GL261-NS cells on treatment with neovibsanin B. The number of colonies formed by GL261-NS cells on treatment with neovibsanin B, VCR and DMSO were 3.34 ± 1.02, 12.53 ± 3.46 and 61.34 ± 9.89% respectively after 7 days. The flow cytometry revealed a marked increase in apoptotic cell death of GL261-NS cells on treatment with neovibsanin B. The western blots showed a significant decrease in the level of activated caspase-3 on treatment with neovibsanin B after 24 h. In addition, neovibsanin B increased the median survival time of glioma-bearing mice (P < 0.05). Therefore, neovibsanin B effectively inhibits glioma cell viability by inducing apoptosis, and can be a potent therapeutic agent for the treatment of malignant glioma.

Proteasome inhibitor MG-132 induces C6 glioma cell apoptosis via oxidative stress.

AIM: Proteasome inhibitors have been found to suppress glioma cell proliferation and induce apoptosis, but the mechanisms are not fully elucidated. In this study we investigated the mechanisms underlying the apoptosis induced by the proteasome inhibitor MG-132 in glioma cells. METHODS: C6 glioma cells were used. MTT assay was used to analyze cell proliferation. Proteasome activity was assayed using Succinyl-LLVY-AMC, and intracellular ROS level was evaluated with the redox-sensitive dye DCFH-DA. Apoptosis was detected using fluorescence and transmission electron microscopy as well as flow cytometry. The expression of apoptosis-related proteins was investigated using Western blot analysis. RESULTS: MG-132 inhibited C6 glioma cell proliferation in a time- and dose-dependent manner (the IC(50) value at 24 h was 18.5 µmol/L). MG-132 (18.5 µmol/L) suppressed the proteasome activity by about 70% at 3 h. It induced apoptosis via down-regulation of antiapoptotic proteins Bcl-2 and XIAP, up-regulation of pro-apoptotic protein Bax and caspase-3, and production of cleaved C-terminal 85 kDa PARP). It also caused a more than 5-fold increase of reactive oxygen species. Tiron (1 mmol/L) effectively blocked oxidative stress induced by MG-132 (18.5 µmol/L), attenuated proliferation inhibition and apoptosis in C6 glioma cells, and reversed the expression pattern of apoptosis-related proteins. CONCLUSION: MG-132 induced apoptosis of C6 glioma cells via the oxidative stress.