The role of zinc in carcinogenesis
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2016-01-01
Autores
Zapaterini, J. R. [UNESP]
da-Silva, F. R.M. [UNESP]
Maxwell, M.
Barbisan, L. F. [UNESP]
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Zinc is the second most abundant trace element in humans and is essential for the activity of more than 300 enzymes. It affects the conformation of many transcription factors associated with control of cell proliferation, apoptosis, and signaling. Therefore, immune function also depends heavily upon its regulation. Studies of this mineral suggest that alterations in zinc homeostasis are linked to the development of numerous diseases, including cancer. Several epidemiologic and experimental studies have investigated the relationship between zinc intake and the risk for development of many cancer types. These include mammary and prostate tumors, and especially cancer of digestive tract. However, experimental outcomes have remained inconsistent. For example, some studies suggest thatincreased zinc intake is negatively associated with colorectal and esophageal cancer, while other studies show a positive or null association. Zinc concentration can affect the body system by many means. In general, zinc effects are based on intermediary metabolism and bioenergetics effects, proliferative/apoptotic effects and motility and invasive effects. Zinc deficiency adversely affects the immune system, increases oxidative stress, and increases the production of inflammatory cytokines. Mitochondrial accumulation of zinc inhibits aconitase activity, halting citrate oxidation. This results in decreasing the cellular energy production requirement of malignant cells. The physiological zinc levels can also affects intracellular signaling pathways. For example, the high intracellular zinc level inhibits the activity of transcription factor NF-ΚB resulting in promestatastic and proangiogenic molecules reduction. By contrast, zinc deficiency increases perphosphorylation of protein kinase B (Akt), E3 ubiquitin-protein ligase (Mdm2), and reduces nuclear p53 accumulation. Overall, more research into the mechanisms of zinc homeostasis are required to better understand its impact on carcinogenesis. Furthermore, studies that can provide the tissue’s zinc concentration profile in tumorigenesis, will improve our understanding of its role in cancer development.
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Zinc Deficiency: Etiology, Screening Methods and Health Implications, p. 39-80.