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Apoptotic effect of MG-132 on human tongue squamous cell carcinoma
Shuang-feng Chen1, Hai-ying Chen, Xian-bin Liu
1Central Laboratory for Experimental Medicine Liaocheng People's Hospital, Liaocheng and Liaocheng Clinical School of Taishan Medical University, Shandong Province, 252000 China.
Abstract:
The aim of this study was to investigate the apoptotic effect of a proteasome inhibitor MG-132 on Tca-8113, a cell line of human tongue squamous cell carcinoma. Tca-8113 cells were treated with 10, 20, and 30μM of MG-132, or 5μM thapsigargin. Apoptosis rate was determined with annexin V/propidium iodide double staining. Expression of E3ubiquitin-protein ligase was determined by ELISA, and Grp78 and caspase-12 mRNA, and Grp78 and caspase-12 protein was assessed by RT-PCR and Western blot, respectively. Apoptosis was observed 18h after MG-132 treatment. The apoptotic rate in the 10, 20, and 30μM MG-132 group was 13.5, 19.6 and 34.7%, respectively, which was higher than in the thapsigargin (8.5%, P<0.01) or control group (0.5%, P<0.01). The expression of E3 ubiquitin-protein ligase in the 10, 20, and 30μM MG-132 group was 28.75±2.28, 18.16±0.65, 8.85±0.72, respectively, which was lower than in the thapsigargin (38.96±0.33, P<0.05 or 0.01) or control (40.88±4.52, P<0.05 or 0.01) group. The levels of Grp78 and capase-12 mRNA, Grp78 and caspase-12 protein in the MG-132 groups were higher than in the control group (P<0.01). In conclusion, MG-132 induces apoptosis in Tca-8113 cells in a concentration-dependent manner. The MG-132-induced apoptosis may involve downregulation of E3 ubiquitin ligase, and upregulation of Grp78 and caspase-12.
Insights
Proteasome inhibitor MG-132 induces apoptosis in human tongue cancer cells concentration-dependently. This effect may involve decreased E3 ubiquitin ligase and increased Grp78 and caspase-12 expression.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Human tongue squamous cell carcinoma (Tca-8113) is a significant health concern.
- Understanding the molecular mechanisms of cancer cell death is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the apoptotic effects of the proteasome inhibitor MG-132 on Tca-8113 cells.
- To elucidate the molecular pathways involved in MG-132-induced apoptosis.
Main Methods:
- Tca-8113 cells were treated with varying concentrations of MG-132 (10, 20, 30μM) or thapsigargin (5μM).
- Apoptosis was quantified using annexin V/propidium iodide staining.
- Expression levels of E3 ubiquitin-protein ligase, Grp78, and caspase-12 were assessed via ELISA, RT-PCR, and Western blot.
Main Results:
- MG-132 treatment led to a concentration-dependent increase in apoptosis in Tca-8113 cells.
- MG-132 significantly downregulated E3 ubiquitin-protein ligase expression.
- MG-132 upregulated the mRNA and protein levels of Grp78 and caspase-12.
Conclusions:
- MG-132 effectively induces apoptosis in human tongue squamous cell carcinoma Tca-8113 cells.
- The observed apoptosis is concentration-dependent.
- MG-132-induced apoptosis is associated with the downregulation of E3 ubiquitin ligase and upregulation of Grp78 and caspase-12, suggesting these as key players in the apoptotic pathway.
