Abstract
Studies have suggested an important role of the trace element zinc (Zn) in prostate biology and functions. Zn has been shown to exist in very high concentrations in the healthy prostate and is important for several prostatic functions. In prostate cancer (PCa), Zn levels are significantly decreased and inversely correlated with disease progression. Ideally, restoration of adequate Zn levels in premalignant/malignant prostate cells could abort prostate malignancy. However, studies have shown that Zn supplementation is not an efficient way to significantly increase Zn concentrations in PCa. Based on a limited number of investigations, the reason for the lower levels of Zn in PCa is believed to be the dysregulation of Zn transporters (especially ZIP and ZnT family of proteins), metallothioneins (for storing and releasing Zn), and their regulators (e.g., Zn finger transcription factor RREB1). Interestingly, the level of Zn in cells has been shown to be modulated by naturally occurring dietary phytochemicals. In this review, we discussed the effect of selected phytochemicals (quercetin, resveratrol, epigallocatechin-3-gallate and curcumin) on Zn functioning and proposes that Zn in combination with specific dietary phytochemicals may lead to enhanced Zn bioaccumulation in the prostate, and therefore, may inhibit PCa.
Highlights
Based on the studies available, we propose that Zn in combination with specific dietary phytochemicals may lead to enhanced Zn bioaccumulation in the prostate, and may inhibit Prostate cancer (PCa)
The importance of Zn homeostasis in PCa can be understood from the fact that there have been no confirmed cases of PCa in which Zn levels are not depleted [3]
Multiple in vitro or in vivo studies suggest that the level of Zn in the system is modulated by naturally occurring dietary phytochemicals
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Studies have shown that prostate cells accumulate high levels of Zn, resulting in inhibition of mitochondrial aconitase, and truncation of Krebs cycle at the first step of citrate oxidation, causing citrate to be the final product. In the absence of high Zn levels, mitochondrial aconitase is not inhibited and citrate oxidation proceeds in the Krebs cycle. This makes malignant cells more bioenergetically efficient than normal prostate cells (reviewed in [3,4]). The depleted concentrations of Zn have been shown to be related to prostate malignancy, and adequate Zn levels if able to reach the prostate may halt PCa progression. Based on the studies available, we propose that Zn in combination with specific dietary phytochemicals may lead to enhanced Zn bioaccumulation in the prostate, and may inhibit PCa
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