Zinc is a group IIB heavy metal. It is an important regulator of major cell signaling pathways in most mammalian cells, functions as an antioxidant and plays a role in maintaining genomic stability. Zinc deficiency leads to severe diseases in the brain, pancreas, liver, kidneys and reproductive organs. Zinc loss occurs during tumor development in a variety of cancers. The prostate normally contains abundant intracellular zinc and zinc loss is a hallmark of the development of prostate cancer development. The underlying mechanism of this loss is not clearly understood. The knowledge that excess zinc prevents the growth of prostate cancers suggests that zinc-mediated therapeutics could be an effective approach for cancer prevention and treatment, although challenges remain. This review summarizes the specific roles of zinc in several cancer types focusing on prostate cancer. The relationship between prostate cancer and the dysregulation of zinc homeostasis is examined in detail in an effort to understand the role of zinc in prostate cancer.Int. J. Mol. Sci. 2020, 21, 2991 2 of 18 in K562 leukemia cells [11]. Withdrawal of zinc from PrEC prostate epithelial cells also stimulates breakage of single-strand DNA [12]. In addition, genes related to DNA damage response, including tumor protein p73 and MRE11, were downregulated in these cells, whereas the expression of p53 was increased. In murine fibroblasts, the addition of zinc can stimulate DNA synthesis and mitogenic signaling, whereas withdrawal of zinc reduces the secretion of growth hormone [13,14]. In Swiss 3T3 fibroblasts, ZnSO 4 can reverse the inhibitory effect of diethylenetrinitrilopentaacetate (DTPA) on thymidine incorporation into DNA, suggesting that zinc stimulates cell growth by regulating cell cycle at the G1/S phase [15]. Intracellular zinc can block the G2/M transition in human bronchial epithelial cells by upregulating p53 and p21 activity [16]. These collective findings highlight the central role of zinc in the modulation of cell proliferation, mainly by affecting DNA synthesis. Therefore, zinc homeostasis plays a key role in the development of many diseases, in which the alteration of zinc is a common event.
Zinc BiologyThe human body mass contains more than 2 g of zinc. Over 90% is distributed to most tissues, with only approximately 0.1% of this metal ion circulating in plasma [17,18]. Yet, this small amount of zinc plays an important role in maintaining homeostasis in the body. Zinc is stored in most organs and tissues with approximately 60% in skeletal muscle, 30% in bone and 5% in liver and skin and the remainder distributed in other tissues that include the brain, kidneys, pancreas and heart [19] (Figure 1). Excess zinc is primarily released through gastrointestinal secretion and endogenous excretion, with minor loss through urinary excretion. Although zinc is an essential trace element used by many enzymes and transcription factors, high concentrations are toxic to the cells. Cells adapt to overcome the toxicity by maintaining the balance of ...
