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

Abstract

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 To 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 these 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 chemopreventive action truly exists.

The bioactivity and applications of pomegranate peel extract: A review

“…EA has a positive effect on the prevention and treatment of cancer. EA can prevent and control the occurrence of cancer through four aspects: (1) Inducing apoptosis of cancer cells; EA can induce and promote the apoptosis of esophageal squamous cell carcinoma (ESCC) cells (Valenzano et al, 2021), and prostate cancer cells (Deng et al, 2017); (2) Inhibition of cancer cell growth; EA can inhibit the growth of human hepatoma cells (HepG2 cells) in G0/G1 phase (Song, Li, et al, 2016), and inhibit the proliferation of cervical cancer cells (Guo et al, 2016); (3) Inhibit the invasion of cancer cells; EA plays an important role by inhibiting the invasion of gastric cancer (GC) cells; (4) Inhibit the expression of enzymes in cancer cells; During the treatment of breast cancer, EA down‐regulates the expression of cyclin‐dependent kinase 6 (CDK6) in breast cancer cell lines (Mişe et al, 2014).…”

“…EA has a positive effect on the prevention and treatment of cancer. EA can prevent and control the occurrence of cancer through four aspects: (1) Inducing apoptosis of cancer cells; EA can induce and promote the apoptosis of esophageal squamous cell carcinoma (ESCC) cells (Valenzano et al, 2021), and prostate cancer cells (Deng et al, 2017);…”

Chemoprevention in Barrett’s esophagus and esophageal adenocarcinoma

“…In a pilot placebo-controlled trial of 10 BE patients, oral zinc supplementation for 2 weeks showed increased apoptosis, upregulation of tumor suppressor mRNAs, a decreased inflammatory state, and decreased epithelial-to-mesenchymal transition signaling in the cells. 41 …”

Cancer Prevention in Patients with GERD and Barrett’s Esophagus—Medicine

“…Observational studies have consistently shown a protective association between vitamin D, 123 polyunsaturated fatty acids (PUFAs), especially n-6 PUFAs, 124 zinc gluconate, 125 and cancer incidence. As a consequence, the use of dietary supplements of these nutraceuticals for chemoprevention in patients with Barrett’s esophagus is being explored.…”

“…After controlling for multiple covariates, Barrett's patients who took 1 or more multivitamin pills a day had a significantly decreased risk of tetraploidy compared to those not taking multivitamins. Significant inverse associations were also observed between risk of EAC and supplemental vitamin C and vitamin E. 122 Observational studies have consistently shown a protective association between vitamin D, 123 polyunsaturated fatty acids (PUFAs), especially n-6 PUFAs, 124 zinc gluconate, 125 and cancer incidence. As a consequence, the use of dietary supplements of these nutraceuticals for chemoprevention in patients with Barrett's esophagus is being explored.…”