Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, CZ-62500 Brno, Czech Republic-European Union.
Curr Med Chem. 2011;18(33):5041-51. doi: 10.2174/092986711797636126.
Zinc(II) ions contribute to a number of biological processes e.g. DNA synthesis, gene expression, enzymatic catalysis, neurotransmission, and apoptosis. Zinc(II) dysregulation, deficiency and over-supply are connected with various diseases, particularly cancer. 98 % of human body zinc(II) is localized in the intracellular compartment, where zinc(II) is bound with low affinity to metallothionein (MT). Zinc transporters ZIP and ZnT maintain transmembrane transport from/to cells or organelles. Imbalance of their regulation is described in cancers, particularly prostate (down-regulated zinc transporters ZIP1, 2, 3 and ZnT-2) and breast, notably its high-risk variant (up-regulated ZIP6, 7, 10). As a result, intracellular and even blood plasma zinc(II) levels are altered. MT protects cells against oxidative stress, because it cooperates with reduced glutathione (GSH). Recent studies indicate elevated serum level of MT in a number of malignancies, among others in breast, and prostate. MT together with zinc(II) affect apoptosis and proliferation, thus together with its antioxidative effects it may affect cancer. To date, only little is known about the influence of zinc(II) and MT on cancer, while these compounds may play an important role in pathogenesis. This review concludes current data regarding the impact of zinc(II) on the pathogenesis of breast and prostate cancers with potential outlines of new, targeted therapy and prevention. Moreover, blood plasma zinc(II) and MT levels and dietary zinc(II) intake are discussed in relation to breast and prostate cancer risk.
锌离子参与多种生物过程，例如 DNA 合成、基因表达、酶催化、神经传递和细胞凋亡。锌离子的失调、缺乏和过量供应与各种疾病有关，特别是癌症。人体 98%的锌离子位于细胞内区室，在细胞内区室中，锌离子与低亲和力结合到金属硫蛋白（MT）上。锌转运蛋白 ZIP 和 ZnT 维持细胞内外的跨膜运输或细胞器。它们的调节失衡在癌症中被描述，特别是前列腺（下调的锌转运蛋白 ZIP1、2、3 和 ZnT-2）和乳腺癌，特别是其高危变体（上调的 ZIP6、7、10）。结果，细胞内甚至血浆锌离子水平发生改变。MT 与还原型谷胱甘肽（GSH）合作保护细胞免受氧化应激。最近的研究表明，许多恶性肿瘤，包括乳腺癌和前列腺癌，血清 MT 水平升高。MT 与锌离子共同影响细胞凋亡和增殖，因此除了其抗氧化作用外，它可能还会影响癌症。迄今为止，人们对锌离子和 MT 对癌症的影响知之甚少，而这些化合物可能在发病机制中发挥重要作用。本综述总结了目前关于锌离子对乳腺癌和前列腺癌发病机制影响的相关数据，并提出了新的靶向治疗和预防的潜在思路。此外，还讨论了血浆锌离子和 MT 水平以及膳食锌离子摄入与乳腺癌和前列腺癌风险的关系。
