Selenium and Cancer inhibition硒与癌症抑制

Selenium and Cancer inhibition

硒与抑制癌症

Selenium, an essential nutritional trace element, has been known to be an essential component in the enzymatic active site of GPX , one of the key enzymes involved in detoxification of hydrogen peroxide (1). Recent studies have demonstrated that selenium is also an essential element of Trx Rs of the Trx redox system, which has been shown to have multiple functions, including regulating cell growth and apoptosis (2, 3). In addition, selenium compounds have been demonstrated to have antitumorigenic activities in animal models by inhibiting tumor initiation and promotion (4) . Selenium compounds inhibit the growth of a variety of tumor cells in vitro via the induction of apoptosis (5, 6, 7) . Epidemiological studies have suggested that low serum selenium levels were associated with an increase in the incidence of cancer (8, 9, 10) . Recent clinical trials showed that supplemental selenium reduced the incidence and mortality of at least five types of human cancers, including prostate cancer (11, 12, 13) . A recent epidemiological study also showed that high levels of toenail selenium were associated with lower incidence and slower progression of human prostate cancer (14) .

硒，一种必不可少的微量营养元素，被认为是GPX（一种参与过氧化氢排毒机制的关键酶）的酶活性位点的重要组成部分（1）。最近的研究表明，硒也是Trx Rs（硫氧还蛋白，硫氧还蛋白氧化还原系统）中必不可少的元素，Trx Rs已被证明具有包含调节细胞生长和凋亡在内的多种功能（2，3）。此外，在动物模型下，硒化合物已被证明可通过抑制肿瘤的发生和发展来显现其抗肿瘤活性的作用（4）。硒化合物通过诱导细胞凋亡（Apoptosis）来抑制各种肿瘤细胞的生长（5，6，7）。流行病学研究表明，血清中硒含量较低的人群，肿瘤发病率较高（8，9，10）。最近的临床试验表明，补充硒可降低至少五种类型的癌症的发病率和死亡率，包括前列腺癌（11，12，13）。最近的一项流行病学研究也表明，趾端硒含量较高

的人群，前列腺癌发病率较低（14）。

Selenium has been well known as a nutritional requirement in maintaining human and animal health. The most important function of selenium in human health is its antioxidant activity resulting from its presence in the enzymatic active site of GPX (1) and Trx Rs (2). This antioxidant function of selenium is also considered to be the probable mechanism of cancer prevention. Evidence supporting this hypothesis was provided from epidemiological studies, which demonstrated that people with low levels of plasma selenium had high incidence of cancer (8, 9, 10). However, animal studies and clinical trials in humans (11) showed that the dosages of selenium required for cancer prevention were at least 10 times higher than that of dietary requirements necessary to reach optimal antioxidant activity. Protection of DNA damage from oxidation by GPX has been considered to be the potential mechanism by which selenium prevents tumor initiation (4) .

众所周知，硒在维护人类和动物健康方面不可或缺。硒在人类健康最重要的功能和价值体现在其强大的抗氧化活性（1）、（2）。硒的这种抗氧化功能也被认为是预防癌症的重要机制。流行病学研究为这一假设提供证据支持，血浆中硒水平较低的人群有较高的癌症发病率（8，9，10）。然而，动物研究和临床试验（11）表明，要预防癌症，硒的剂量需要至少饮食中获取量的10倍以上，才能达到最佳的抗氧化活性。通过GPX保护DNA的氧化损伤被认为是硒防止肿瘤启动的潜在机制（4）。

In addition to its antioxidant activity, selenium is known to be toxic at high levels, which is proposed to be one of the possible anticancer mechanisms. When selenite undergoes redox metabolism, GSH is consumed, whereas GSSG and ROS, especially superoxide, are produced (7). This can shift the cellular redox balance to a relative oxidative state. This change may result in two possible consequences to cells, depending on the dose, duration, and intracellular detoxifying systems: (a) it may