Insight to Physiology and Pathology of Zinc(II) Ions and Their Actions in Breast and Prostate Carcinoma

Abstract

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.

Metallothioneins and zinc in cancer diagnosis and therapy

“…MREs are located in the promoter regions of MT genes (Gunes et al, 1998) and are present in multiple copies in the promoter/enhancer regions of almost all metal-inducible MTs (Culotta and Hamer, 1989;Searle et al, 1985). However, there have been identified other metals, which are able to induce MT transcription and also pose a threat to cells because of their ability to promote carcinogenetic processes, such as Cd 2+ (Il'yasova and Schwartz, 2005;Waalkes and Rehm, 1994), Cr 6+ , and Ni 2+ (Seo et al, 2005;Gumulec et al, 2011). One of their adverse actions is displacing zinc from zinc-saturated MTs or other zincbinding proteins.…”

“…Most work is focused on the immunohistochemical determination of MTs in tumors Babula et al, 2011;Eckschlager et al, 2009;Gumulec et al, 2011;Krizkova et al, 2008Krizkova et al, , 2009Krizkova et al, , 2010Krizkova et al, , 2012Sochor et al, 2012), but also on its determination in serum by various methods, such as Brdicka's reaction or enzymelinked immonosorbent assay Krizkova et al, 2010). MT can serve as a prognostic marker in central nervous system tumors of childhood and adolescence (Rickert and Paulus, 2005;Rickert, 2004), osteosarcoma (Trieb and Kotz, 2001), breast cancer (Woolston et al, 2010;Jin et al, 2004;Gomulkiewicz et al, 2010), pancreatic islet cell tumors (Tomita, 2002), and tongue squamous-cell carcinoma (Theocharis et al, 2011).…”

Bacteriolyses of Bacterial Cell Walls by Cu(II) and Zn(II) Ions Based on Antibacterial Results of Dilution Medium Method and Halo Antibacterial Test

“…Hence, the zinc homeostasis with apoptosis and necrosis for cancer cell should be eventually established. It has become apparent that zinc ions inhibit mitochondoria [5], lysosomes [6], DNA [7], and nucleus [8] of cancer cell, and that regulate cell proliferation and growth [9,10], and metastasis [11]of tumor cell. However, no confirmed common relationships of zinc ions with cancer development and progression have been identified, in which killing mechanisms of cancer cell and tumor cell by Cu 2+ , Zn 2+ ions are not yet definitely elucidated.…”

Zinc transporters and dysregulated channels in cancers

“…Although serum or plasma Zn is not a good biomarker for Zn deficiency, there is compelling evidence that dysregulated Zn homeostasis is indeed associated with many cancers. Multiple studies show that serum Zn levels are generally low in patients with certain cancers, including esophageal squamous cell carcinoma (ESCC) (75–78), malignant prostate cancer (79, 80), breast cancer (79), ovarian cancer, and so on (81–83). Normal physiological concentrations of Zn inhibit cancer cell proliferation and migration, maintain balanced metabolism and promote apoptosis in cancer cells.…”