Abstract
The Vitamin E family contains α-, β-, γ- and δ-tocopherol (αT, βT, γT and δT) and α-, β-, γ- and δ-tocotrienol (αTE, βTE, γTE and δTE). Research has revealed distinct roles of these vitamin E forms in prostate cancer (PCa). The ATBC trial showed that αT at a modest dose significantly decreased PCa mortality among heavy smokers. However, other randomized controlled trials including the SELECT trial indicate that supplementation of high-dose αT (≥ 400IU) does not prevent PCa among non-smokers. Preclinical cell and animal studies also do not support chemopreventive roles of high-dose αT and offer explanations for increased incidence of early-stage PCa reported in the SELECT study. In contrast, accumulating animal studies have demonstrated that γT , δT, γTE and δTE appear to be effective for preventing early-stage PCa from progression to adenocarcinoma in various PCa models. Existing evidence also support therapeutic roles of γTE and its related combinations against advanced PCa. Mechanistic and cell-based studies show that different forms of vitamin E display varied efficacy, i.e., δTE ≥ γTE > δT ≥ γT >> αT, in inhibiting cancer hallmarks and enabling characteristics, including uncontrolled cell proliferation, angiogenesis and inflammation possibly via blocking 5-lipoxygenase, NF-κB, HIF-1α, modulating sphingolipids, and targeting PCa stem cells. Overall, existing evidence suggests that modest αT supplement may be beneficial to smokers, and γT, δT, γTE and δTE are promising agents for PCa prevention for modest- to relatively high-risk population. Despite encouraging preclinical evidence, clinical research testing γT, δT, γTE and δTE for PCa prevention is sparse and should be considered.
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