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Published on: June 23, 2018
Proteasome inhibitor MG-132 induces C6 glioma cell apoptosis via oxidative stress
Wen-hai Fan1, Yi Hou, Fan-kai Meng
1Department of Neurosurgery, 1st Bethune Hospital of Jilin University, Changchun 130021, China.
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.
Insights
The proteasome inhibitor MG-132 suppresses glioma cell proliferation and induces apoptosis by increasing oxidative stress. This mechanism involves regulating apoptosis-related proteins and is counteracted by antioxidants.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Proteasome inhibitors show potential in suppressing glioma cell proliferation and inducing apoptosis.
- The precise mechanisms underlying MG-132-induced apoptosis in glioma cells require further elucidation.
Purpose of the Study:
- To investigate the mechanisms responsible for apoptosis induced by the proteasome inhibitor MG-132 in C6 glioma cells.
Main Methods:
- Cell proliferation was assessed using MTT assays.
- Proteasome activity and intracellular reactive oxygen species (ROS) levels were measured.
- Apoptosis was detected via microscopy and flow cytometry, with protein expression analyzed by Western blot.
Main Results:
- MG-132 inhibited C6 glioma cell proliferation and proteasome activity in a time- and dose-dependent manner.
- MG-132 induced apoptosis by altering the expression of Bcl-2, XIAP, Bax, caspase-3, and PARP, and significantly increased ROS levels.
- The antioxidant Tiron mitigated MG-132's effects on proliferation, apoptosis, and protein expression, indicating a role for oxidative stress.
Conclusions:
- MG-132 induces apoptosis in C6 glioma cells primarily through the mechanism of oxidative stress.
- Targeting oxidative stress pathways may offer therapeutic strategies for glioma treatment.
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