Brigelius-Flohé Regina
Department Biochemistry of Micronutrients, German Institute of Human Nutrition, Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, D-14558 Nuthetal.
Chem Biodivers. 2008 Mar;5(3):389-95. doi: 10.1002/cbdv.200890039.
An adequate selenium (Se) status has for long been considered to prevent the development of various forms of cancer. However, underlying molecular mechanisms remained unknown. In mammals, selenium exerts its functions as selenocysteine incorporated into selenoproteins. Therefore, Se compounds can either act as Se source for selenoproteins or, depending on their chemical forms, in distinct ways. Most potent chemopreventive effects have been attributed to compounds in which the Se moiety is methylated. These compounds are able to induce phase 2 enzymes which are involved in the cellular defense system that is regulated by the Nrf2 transcription factor. Selenoproteins best studied in cancer development are members of the glutathione peroxidase (GPx) and thioredoxin reductase (TrxR) family. In various cancer cells and tissues, GPx2 and/or TrxR1 are up-regulated. Interestingly, both enzymes are targets of Nrf2. An enhanced expression of these enzymes may represent a mechanism to counteract carcinogenic pathways. They may, however, also provide a selective advantage for pre-existing tumor cells in guaranteeing survival and continuous proliferation.
长期以来，充足的硒（Se）状态被认为可预防多种癌症的发生。然而，其潜在的分子机制仍不清楚。在哺乳动物中，硒以硒代半胱氨酸的形式掺入硒蛋白发挥其功能。因此，硒化合物既可以作为硒蛋白的硒源，也可以根据其化学形式以不同的方式发挥作用。最有效的化学预防作用归因于硒部分被甲基化的化合物。这些化合物能够诱导参与由Nrf2转录因子调节的细胞防御系统的Ⅱ相酶。在癌症发生过程中研究最多的硒蛋白是谷胱甘肽过氧化物酶（GPx）和硫氧还蛋白还原酶（TrxR）家族的成员。在各种癌细胞和组织中，GPx2和/或TrxR1上调。有趣的是，这两种酶都是Nrf2的靶点。这些酶表达的增强可能代表一种对抗致癌途径的机制。然而，它们也可能为已存在的肿瘤细胞提供选择性优势，以保证其存活和持续增殖。
