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McCarty et al. J Cancer Metastasis Treat 2020;6:20 Journal of Cancer
DOI: 10.20517/2394-4722.2020.47 Metastasis and Treatment

Commentary Open Access

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

Mark F. McCarty , Simon Iloki Assanga , Lidianys Lewis Lujan 2
2
1
1 Catalytic Longevity Foundation, San Diego, CA 92109, USA.
2 Department of Research and Postgraduate in Food, University of Sonora, Hermosillo 83210, Mexico.
Correspondence to: Mark F. McCarty, President, Catalytic Longevity Foundation, 811 B Nahant Ct, San Diego, CA 92109, USA.
E-mail: markfmccarty@gmail.com
How to cite this article: McCarty MF, Iloki-Assanga S, Lujan LL. Could zinc dipicolinate be used to “smuggle” zinc into prostate
cancer cells? J Cancer Metastasis Treat 2020;6:20. http://dx.doi.org/10.20517/2394-4722.2020.47
Received: 17 May 2020 First Decision: 24 Jun 2020 Revised: 24 Jun 2020 Accepted: 6 Jul 2020 Published: 19 Jul 2020

Academic Editor: Rafat A. Siddiqui Copy Editor: Cai-Hong Wang Production Editor: Jing Yu

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

© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0
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