Improvement of Antiproliferative Activity of Recombinant Truncated Form of Pseudomonas aeruginosa Exotoxin (PE38) by Vitamin E in MCF-7 Cells

Background: In addition to beneficial roles of vitamin E in many metabolic processes and its antitumor activities, vitamin E derivatives have extensively been considered as permeability enhancers. Using these enhancers, permeability of a wide spectrum of drugs was reported to be significantly increased. PE38, a toxic substance with a potential application in cancer therapy, is a truncated form of Pseudomonas exotoxin A (PE), which lacks Ia and a portion of domain Ib. Objective: Here, the antiproliferative potential of PE38 and alpha-tocopherol (αT) form of vitamin E were assessed in MCF-7 cells. The role of vitamin E in PE38 cytotoxicity level was also evaluated. Materials and Methods: The antiproliferative potential of PE38, vitamin E, and a combination of them were colorimetrically evaluated in a cellular breast cancer model (MCF-7), using the MTT assay. P values of <0.05 were considered significant. Results: Compared to control cells, the PE38 inhibited the proliferation of MCF-7 cells (80% ± 1.37% cell viability) only at the highest concentration used (500 μg/mL) (P < 0.05). MTT assay also showed that 0.1, 1, and 10mg/mL of vitamin E could significantly (P < 0.001) decrease the cell viability of MCF-7 cells to 57% ± 1.37%, 26.8% ± 1.37%, and 14.7% ± 1.37% at 24 h, respectively. Moreover, the coadministration of vitamin E (0.1 mg/mL) with 31.25, 62.5, 125, 250, and 500 μg/mL concentrations of PE38 decreases in cell viability from 100% in control cells to 35.61% ± 4.29%, 37.8% ± 6.45%, 36.42% ± 5.79%, 32.33% ± 4.62%, and 29.97% ± 5.07% at 24 h, respectively (P < 0.001). Conclusion: The results of this study suggest that vitamin E can enhance the antiproliferative activity of PE38 toward MCF-7 cells.