Zinc Gluconate Induces Potentially Cancer Chemopreventive Activity in Barrett’s Esophagus: A Phase 1 Pilot Study

Autor: K. Leroy, Elizabeth Rybakovsky, James M. Mullin, S. McShane, P. Wong, Erin McDonnell, S. Trembeth, Mary Carmen Valenzano, Elizabeth Richardson, James J Thornton, Ryan Urbas, Jared Lander, Jonathan M. Raines, A. Corcoran, S. Yalamanchili, William Huntington, Gary Newman, B. Etemad, V. Chen, Giancarlo Mercogliano, Marc Zitin, Andrew V. Kossenkov, Louise Y.Y. Fong, Barani Mayilvaganan, A. Mathew, Laura Connor, Gary Daum
Rok vydání: 2020
Předmět:
Zdroj: Dig Dis Sci
ISSN: 1573-2568
0163-2116
Popis: BACKGROUND: Chemopreventive effects of zinc for esophageal cancer have been well documented in animal models. This prospective study explores if a similar, potentially chemopreventive action can be seen in Barrett’s esophagus (BE) in humans. AIMS: Determine if molecular evidence can be obtained potentially indicating zinc’s chemopreventive action in Barrett’s metaplasia. METHODS: Patients with a prior BE diagnosis were placed on oral zinc gluconate (14 days of 26.4 mg zinc BID) or a sodium gluconate placebo, prior to their surveillance endoscopy procedure. Biopsies of Barrett’s mucosa were then obtained for miRNA and mRNA microarrays, or protein analyses. RESULTS: Zinc-induced mRNA changes were observed for a large number of transcripts. These included downregulation of transcripts encoding proinflammatory proteins (IL32, IL1β, IL15, IL7R, IL2R, IL15R, IL3R), upregulation of anti-inflammatory mediators (IL1RA), downregulation of transcripts mediating epithelial-to-mesenchymal transition (EMT) (LIF, MYB, LYN, MTA1, SRC, SNAIL1 and TWIST1) and upregulation of transcripts that oppose EMT (BMP7, MTSS1, TRIB3, GRHL1). miRNA arrays showed significant upregulation of seven miRs with tumor suppressor activity (−125b-5P, −132-3P, −548z, −551a, −504, −518 and −34a-5P). Of proteins analyzed by western blot, increased expression of the pro-apoptotic protein, BAX, and the tight junctional protein, CLAUDIN-7, along with decreased expression of BCL-2, and VEGF-R2, were noteworthy. CONCLUSIONS: When this mRNA, miRNA and protein molecular data are considered collectively, a cancer-chemopreventive action by zinc in Barrett’s metaplasia may be possible for this precancerous esophageal tissue. These results and the extensive prior animal model studies argue for a future prospective clinical trial for this safe, easily-administered and inexpensive micronutrient, that could determine if a chemopreventitive action truly exists.
Databáze: OpenAIRE
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