PDF(Pubmed)
Abstract：
The vitamin E family contains α-tocopherol (αT), βT, γT, and δT and α-tocotrienol (TE), 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 Selenium and Vitamin E Cancer Prevention Trial (SELECT) indicate that supplementation of high-dose αT (≥400 IU) does not prevent PCa among nonsmokers. 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. 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, that is, δTE ≥ γTE > δT ≥ γT >> αT, in inhibiting cancer hallmarks and enabling characteristics, including uncontrolled cell proliferation, angiogenesis, and inflammation possibly via blocking 5-lipoxygenase, nuclear factor κB, hypoxia-inducible factor-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-risk 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.
摘要：
维生素E家族含有α-，β-,γ-和δ-生育酚(αT，βT,γT和δT)和α-，β-,γ-和δ-生育三烯酚(αTE，βTE,γTE和δTE)。研究揭示了这些维生素E形式在前列腺癌（PCa）中的不同作用。ATBC试验表明，适度剂量的αT可显着降低重度吸烟者的PCa死亡率。然而,包括SELECT试验在内的其他随机对照试验表明,在非吸烟者中,补充大剂量αT(≥400IU)并不能预防PCa.临床前细胞和动物研究也不支持高剂量αT的化学预防作用，并提供SELECT研究中报道的早期PCa发病率增加的解释。相比之下,积累的动物研究表明，γT，δT,在各种PCa模型中，γTE和δTE似乎可有效预防早期PCa进展为腺癌。现有证据也支持γTE及其相关组合对晚期PCa的治疗作用。机制和基于细胞的研究表明，不同形式的维生素E表现出不同的功效，即，δTE≥γTE>δT≥γT>>αT，在抑制癌症标志和使能特征方面，包括不受控制的细胞增殖，血管生成和炎症可能通过阻断5-脂氧合酶，NF-κB,HIF-1α,调节鞘脂，靶向PCa干细胞。总的来说,现有证据表明，适度补充αT可能对吸烟者有益，和γT,δT,γTE和δTE是预防高危人群PCa的有前途的药物。尽管临床前证据令人鼓舞，临床研究测试γT，δT,预防PCa的γTE和δTE稀疏，应予以考虑。
