δ-Tocotrienol Potentiates Breast and Prostate Cancer Cells to Paclitaxel via Suppressing PD-L1-Mediated Cancer-Promoting Signaling

Abstract

Vitamin E can exert either a cancer preventive effect or improve the therapeutic efficacy of chemotherapeutic drugs against multiple types of cancer. Ample evidence suggests that the cancer preventive activity of vitamin E is form-dependent; however, it is not clear whether its chemosensitization effect is also influenced by its forms. The objectives of this study were to investigate whether the eight natural forms of vitamin E produced differential sensitization effects on cancer chemotherapeutic drugs and to address whether the chemosensitization effect of vitamin E was associated with its inhibitory effect on programmed cell death ligand 1 (PD-L1) signaling. We carried out a comparative evaluation of the chemosensitization effect of eight vitamin E forms using paclitaxel as a representative therapeutic drug and breast/prostate cancer as the representative types of cancer. Results showed that the sensitization effect of vitamin E on chemotherapeutic drugs was also form-dependent, with δ-tocotrienol (δ-T3) as the most effective one for sensitizing breast and prostate cancer cells to paclitaxel, mechanistically associated with its ability to suppress PD-L1-mediated tumor-promoting signaling. The findings provided novel insights into understanding the sensitization effect of vitamin E and its related mechanisms and support that δ-T3 is the best candidate as an enhancer of taxanes among the eight forms.