Department of Chemistry and Biochemistry, Faculty of Agronomy, Mendel University in Brno, Brno, Czech Republic.
Drug Metab Rev. 2012 Dec;44(4):287-301. doi: 10.3109/03602532.2012.725414. Epub 2012 Oct 11.
Metallothioneins (MTs) are involved in protection against oxidative stress (OS) and toxic metals and they participate in zinc metabolism and its homeostasis. Disturbing of zinc homeostasis can lead to formation of reactive oxygen species, which can result in OS causing alterations in immunity, aging, and civilization diseases, but also in cancer development. It is not surprising that altered zinc metabolism and expression of MTs are of great interest in the case of studying of oncogenesis and cancer prognosis. The role of MTs and zinc in cancer development is tightly connected, and the structure and function of MTs are strongly dependent on Zn²⁺ redox state and its binding to proteins. Antiapoptic effects of MTs and their interactions with proteins nuclear factor kappa B, protein kinase C, esophageal cancer-related gene, and p53 as well as the role of MTs in their proliferation, immunomodulation, enzyme activation, and interaction with nitric oxide are reviewed. Utilization of MTs in cancer diagnosis and therapy is summarized and their importance for chemoresistance is also mentioned.
金属硫蛋白（MTs）参与保护机体免受氧化应激（OS）和有毒金属的侵害，参与锌代谢及其体内平衡。锌代谢平衡的破坏会导致活性氧的形成，从而导致 OS，引起免疫、衰老和文明疾病的改变，也会导致癌症的发展。因此，改变锌代谢和 MTs 的表达在研究致癌作用和癌症预后方面引起了极大的关注，这并不奇怪。MTs 和锌在癌症发展中的作用紧密相连，MTs 的结构和功能强烈依赖于 Zn²⁺的氧化还原状态及其与蛋白质的结合。本文综述了 MTs 的抗凋亡作用及其与核因子 kappa B、蛋白激酶 C、食管癌相关基因和 p53 等蛋白质的相互作用，以及 MTs 在增殖、免疫调节、酶激活以及与一氧化氮相互作用中的作用。总结了 MTs 在癌症诊断和治疗中的应用，并提到了它们对化疗耐药性的重要性。
