Role of zinc in the pathogenesis and treatment of prostate cancer: critical issues to resolve - PubMed (original) (raw)

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Role of zinc in the pathogenesis and treatment of prostate cancer: critical issues to resolve

L C Costello et al. Prostate Cancer Prostatic Dis. 2004.

Abstract

The most consistent and persistent biochemical characteristic of prostate cancer (PCa) is the marked decrease in zinc and citrate levels in the malignant cells. This relationship provides compelling evidence that the lost ability of the malignant cells to accumulate zinc is an important factor in the development and progression of prostate malignancy. In addition, this relationship provides a rational basis for the concept that restoration of high zinc levels in malignant cells could be efficacious in the treatment and prevention of PCa. Epidemiological studies regarding dietary zinc effects on PCa have been conflicting and confusing. The purpose of this presentation is to present a current state of information regarding zinc relationships in the pathogenesis and treatment of PCa. We also hope to bring more attention to the medical and research community of the critical need for concerted clinical and basic research regarding zinc and PCa.

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Figures

Figure 1

Role of zinc in the pathway of net citrate production.

Figure 2

Mechanism of zinc-induced mitochondrial apoptogenesis in prostate cells.

Figure 3

Composite results of zinc and citrate levels in prostate cancer, benign hyperplasia, and normal individuals. The citrate values were determined by in situ magnetic resonance spectroscopy of the prostate. The zinc values were determined by energy dispersive X-ray fluorescence of resected prostate tissue.

Figure 4

Concept of pathogenesis of prostate malignancy. The normal cell possesses the zinc-accumulating apparatus (ZIP1). The high zinc levels in mitochondria inhibit m-aconitase resulting in the inability to oxidize citrate and the accumulation of citrate. The neoplastic cell has lost the ability to accumulate zinc. As the cellular zinc levels are decreased in the premalignant cell, citrate oxidation occurs with the concurrent increased production of ATP. The malignant cell is now metabolically and energetically capable of proceeding with its malignant process. Another effect (not shown in this figure) of the decrease in zinc is the removal of its apoptogenic effect, which then permits the proliferation of the malignant cells.

Figure 5

Effect of zinc treatment of mice on PC-3 tumor growth. (a) Tumor growth. (b) Tumor zinc level. (c) Tumor citrate level. (d) Tumor cell apoptosis.

References

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Role of zinc in the pathogenesis and treatment of prostate cancer: critical issues to resolve - PubMed (original) (raw)