*2.4. T3, TOS, and T3E Enhanced Sensitivity to Bortezomib in H2452*

We next evaluated the effect of bortezomib in combination with TP, T3, TOS, and T3E on cell viability using a WST-8 assay. As shown in Figure 4, the combination groups with bortezomib and T3, TOS, and T3E showed a significant decrease in cell viability compared to the control group, bortezomib alone group, and respective alone groups, suggesting that T3, TOS, and T3E may enhance bortezomib sensitivity.

(**c**)

**Figure 3.** Effects of vitamin E on proteasome activities in the treatment of bortezomib. H2452 cells were treated with bortezomib 50 NM or bortezomib 50 nM +TP 20 μM, T3 20 μM, TOS 20 μM, T3E 20 μM for 6 h (**a**), and another 6 h except for bortezomib (**b**). After the treatment, chymotrypsin-like activity was assessed by a chemiluminescent method, as described in the Materials and Methods section. Data are means ± SD, n = 3. \*\* *p* < 0.01 vs. as indicated. (**c**) H2452 cells were treated with bortezomib 50 nM or bortezomib 50 nM + TP 20 μM, T3 20 μM, TOS 20 μM, and T3E 20 μM for 12 h. After the treatment, ubiquitinated protein levels in each sample were assessed by immunoblotting. α-Tubulin protein levels served as the loading control. Results are representative of three independent experiments. BTZ; bortezomib, TP; α-tocopherol, T3; α-tocotrienol, TOS; α-tocopheryl succinate, T3E; 6-O-Carboxypropyl-alpha-tocotrienol.
