Natural forms of vitamin E and metabolites—regulation of cancer cell death and underlying mechanisms

The disappointing results from large clinical studies of α‐tocopherol (αT), the major form of vitamin E in tissues, for prevention of chronic diseases including cancer have cast doubt on not only αT but also other forms of vitamin E regarding their role in preventing carcinogenesis. However, basic research has shown that specific forms of vitamin E such as γ‐tocopherol (γT), δ‐tocopherol (δT), γ‐tocotrienol (γTE) and δ‐tocotrienol (δTE) can inhibit the growth and induce death of many types of cancer cells, and are capable of suppressing cancer development in preclinical cancer models. For these activities, these vitamin E forms are much stronger than αT. Further, recent research revealed novel anti‐inflammatory and anticancer effects of vitamin E metabolites including 13′‐carboxychromanols. This review focuses on anti‐proliferation and induction of death in cancer cells by vitamin E forms and metabolites, and discuss mechanisms underlying these anticancer activities. The existing in vitro and in vivo evidence indicates that γT, δT, tocotrienols and 13′‐carboxychromanols have anti‐cancer activities via modulating key signaling or mediators that regulate cell death and tumor progression, such as eicosanoids, NF‐κB, STAT3, PI3K, and sphingolipid metabolism. These results provide useful scientific rationales and mechanistic understanding for further translation of basic discoveries to the clinic with respect to potential use of these vitamin E forms and metabolites for cancer prevention and therapy. © 2018 IUBMB Life, 71(4):495–506, 2019