Abstract
Prostate cancer (PCa) is one of the most common cancers and the second leading cause of cancer-related death among men worldwide. Despite progresses in early diagnosis and therapeutic strategies, prognosis for patients with advanced PCa remains poor. Noteworthily, a unique feature of healthy prostate is its highest level of zinc content among all soft tissues in the human body, which dramatically decreases during prostate tumorigenesis. To date, several reviews have suggested antitumor activities of zinc and its potential as a therapeutic strategy of PCa. However, an overview about the role of zinc and its signaling in PCa is needed. Here, we review literature related to the content, biological function, compounds and clinical application of zinc in PCa. We first summarize zinc content in prostate tissue and sera of PCa patients with their clinical relevance. We then elaborate biological functions of zinc signaling in PCa on three main aspects, including cell proliferation, death and tumor metastasis. Finally, we discuss clinical applications of zinc-containing compounds and proteins involved in PCa signaling pathways. Based on currently available studies, we conclude that zinc plays a tumor suppressive role and can serve as a biomarker in PCa diagnosis and therapies.
Highlights
Prostate cancer (PCa) is the most commonly diagnosed cancer and has the second highest death rate among men worldwide, in developed countries [1,2]
Zinc homeostasis in the prostate gland is tightly regulated by two protein families of zinc transporters; the Zrt-Irt-like protein (ZIP) family mediates zinc transport from extracellular fluid or intracellular vesicles into cytoplasm, and the ZnT family is responsible for decreasing cytoplasmic zinc levels by transporting zinc from cytoplasm to the outside of cells or into intracellular vesicles [123,124,125]
These results indicate that ZIP1, a major zinc uptake transporter, functions as a tumor suppressor in PCa, which is consistent with the anti-tumor activity of zinc discussed above
Summary
Prostate cancer (PCa) is the most commonly diagnosed cancer and has the second highest death rate among men worldwide, in developed countries [1,2]. The most common and widely accepted therapeutic options for PCa patients are the combinations of surgery, radiotherapy and hormone therapy [9,10,11] These treatments could lead to side effects and considerable recurrence rates [9]. Zinc was recognized as an intraand intercellular signaling mediator with vital regulatory functions in signal transduction [18,24] Based on those studies, zinc plays a crucial role in various biological events, including antioxidant defense, DNA repair, tissue repair, immunoprotection, wound healing and cell division [18,25]. This review deliberates about the potential of clinical applications to target zinc signaling in PCa therapies
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