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 30 'M of MG-132, or 5 'M 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 18 h after MG-132 treatment. The apoptotic rate in the 10, 20, and 30 'M 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 30 'M 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.