Conversely, other studies have shown that high-dose supplements of zinc can increase the risk of prostate cancer. Thus, the role of dietary zinc in the predisposition to prostate cancer requires further study. The relationship between dietary zinc and prostate cancer
likely stems from the vital role that zinc plays in prostate function. Zinc is known to accumulate in the prostate, and this gland typically harbors the highest concentration of zinc in the body. This is because the secretory cells of the prostate require high levels of zinc to inhibit the enzyme m-aconitase, which normally functions to oxidize citrate during the Krebs cycle. Because citrate is a principle component buy P505-15 of seminal fluid, prostate secretory cells do not complete the oxidation of citrate in the mitochondria and the zinc-mediated inhibition of m-aconitase is crucial for the accumulation of citrate in these cells, and thus the subsequent secretion of citrate into seminal fluid. The accumulation of zinc in the prostate epithelium is accomplished by the zinc transporter ZIP1, which is
highly expressed in normal prostate tissue. Because zinc is thus antagonistic to the synthesis of ATP in the cells of the prostate gland, it is not surprising that both ZIP1 expression and the accumulation of zinc are markedly attenuated in a cancerous prostate . . Indeed, NVP-BSK805 mw ZIP1 is considered a prostate tumor MYO10 suppressor as
the inhibition of its function is requisite for malignant transformation, and prostatic zinc levels have shown an inverse relationship with tumorigenicity . Thus, the restoration of zinc levels in prostate cancer cells is a logical strategy for clinical treatment. Further, zinc has been shown to be required for mitochondrial apoptogenesis in prostate cells in vitro , and infusions of moderate doses of zinc reliably lead to apoptosis of prostate cancer cell lines . This has led to the hypothesis that clinical administration of zinc could be an effective chemotherapeutic for prostate cancer. However, studies of zinc dietary supplementation for cancer prevention have had mixed results [14, 15]. Recently, vascular delivery of zinc was evaluated as a potential treatment in a mouse model of prostate cancer . Although an increase in apoptosis was observed in the prostate cancer xenografts of the mice receiving high doses of zinc, there was little effect on the overall growth and aggressiveness of the prostate tumors themselves. Because ZIP1 function is known to be impaired in prostate cancer cells, we presume that there was limited homing of zinc to the prostate cancer xenografts. Thus, we reason that a localized infusion of zinc, and thus a greater local concentration, could circumvent the reduced ZIP1 activity and allow greater bioaccumulation of zinc in the diseased prostate.