Could zinc dipicolinate be used to “smuggle” zinc into prostate cancer cells?

Abstract

Although prostate epithelium concentrates zinc for the purpose of promoting citrate secretion, it loses its capacity to import zinc while undergoing malignant transformation. This exclusion of zinc may be necessary for the viability of prostate cancer, as measures which increase the intracellular zinc content of prostate cancers lead to cell death, oxidative stress, and a marked reduction in ATP, suggestive of mitochondrial damage. The anti-fungal drug clioquinol, which can act as a zinc ionophore, can markedly slow the growth of human prostate cancer in nude mice, and has been proposed as a clinical therapy for prostate cancer. However, clioquinol is currently only available as a topical agent, as it was linked to subacute myelo-optic neuropathy with oral use. A more practical option for promoting zinc transport may be offered by the nutraceutical zinc dipicolinate, a stable chelate in which four coordination positions of zinc are occupied by two molecules of the tryptophan metabolite picolinic acid. Zinc dipicolinate is a highly effective supplemental source of zinc that has been shown to be more potent than soluble zinc salts for alleviating the symptoms of acrodermatitis enteropathica, a genetic zinc deficiency disorder reflecting homozygous loss of functional ZIP4 zinc importers in enterocytes. This suggests that the zinc dipicolinate complex is sufficiently stable and lipophilic to transfer zinc across cellular membranes. If so, it may have potential for “smuggling” zinc into prostate cancer cells. Hence, cell culture and rodent studies to evaluate the impact of zinc dipicolinate on human prostate cancer are warranted.

Keywords

Prostate cancer / zinc / clioquinol / picolinic acid / ZIP4

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