Nutritional and Zinc Status of Head and Neck Cancer Patients: An Interpretive Review

Prasad, Ananda S.; Beck, Frances W.J.; Doerr, Timothy D.; Shamsa, Falah; Penny, Hayward S.; Marks, Steven C.; Kaplan, Joseph; Küçük, Ömer; Mathog, Robert H.

doi:10.1080/07315724.1998.10718787

Cited by 80 publications

(60 citation statements)

References 26 publications

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“…Dietary Zn deficiency has been linked to many human cancers, including esophageal SCC 10, head and neck 11, and digestive tract cancers 12. Likewise, studies of rodent models of chemically induced esophageal and forestomach cancers have shown that Zn deficiency results in significantly more tumors and more severe histopathological lesions 13, 14.…”

Section: Introductionmentioning

confidence: 99%

Reduction in squamous cell carcinomas in mouse skin by dietary zinc supplementation

Sun

Shen²,

Schrock

et al. 2016

Cancer Medicine

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Inadequate dietary Zn consumption increases susceptibility to esophageal and other cancers in humans and model organisms. Since Zn supplementation can prevent cancers in rodent squamous cell carcinoma (SCC) models, we were interested in determining if it could have a preventive effect in a rodent skin cancer model, as a preclinical basis for considering a role for Zn in prevention of human nonmelanoma skin cancers, the most frequent cancers in humans. We used the 7,12‐dimethyl benzanthracene carcinogen/phorbol myristate acetate tumor promoter treatment method to induce skin tumors in Zn‐sufficient wild‐type and Fhit (human or mouse protein) knockout mice. Fhit protein expression is lost in >50% of human cancers, including skin SCCs, and Fhit‐deficient mice show increased sensitivity to carcinogen induction of tumors. We hypothesized that: (1) the skin cancer burdens would be reduced by Zn supplementation; (2) Fhit −/−(Fhit, murine fragile histidine triad gene) mice would show increased susceptibility to skin tumor induction versus wild‐type mice. 30 weeks after initiating treatment, the tumor burden was increased ~2‐fold in Fhit −/− versus wild‐type mice (16.2 versus 7.6 tumors, P < 0.001); Zn supplementation significantly reduced tumor burdens in Fhit −/− mice (males and females combined, 16.2 unsupplemented versus 10.3 supplemented, P = 0.001). Most importantly, the SCC burden was reduced after Zn supplementation in both strains and genders of mice, most significantly in the wild‐type males (P = 0.035). Although the mechanism(s) of action of Zn supplementation in skin tumor prevention is not known in detail, the Zn‐supplemented tumors showed evidence of reduced DNA damage and some cohorts showed reduced inflammation scores. The results suggest that mild Zn supplementation should be tested for prevention of skin cancer in high‐risk human cohorts.

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Section: Introductionmentioning

confidence: 99%

Reduction in squamous cell carcinomas in mouse skin by dietary zinc supplementation

Sun

Shen²,

Schrock

et al. 2016

Cancer Medicine

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“…Jaiswal and Narayan [43] reported that zinc inhibits the proliferation of colon cancer cells. In head and neck cancers, systemic zinc deficiency was associated with increased tumor size and stage of the cancer [44]. Zinc (and copper) is significantly lower in human hepatoma tissue compared with those in the surrounding "normal" hepatic tissue; and the plasma zinc level is significantly lower in hepatoma subjects compared with the subjects without known liver disease [45].…”

Section: Tumor Suppressor Effects Of Zinc In Other Tumor Cellsmentioning

confidence: 99%

Zinc as an anti-tumor agent in prostate cancer and in other cancers

Franklin¹,

Costello²

2007

Archives of Biochemistry and Biophysics

211

142

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Human prostate glandular epithelial cells have the unique capability of accumulating high levels of zinc. This is essential to inhibit m-aconitase activity so that citrate can accumulate for secretion into prostatic fluid, which is a major function of the prostate gland. As a result, the Krebs cycle is truncated with the consequence of the lost ATP production that would result from citrate oxidation. The cellular accumulation of zinc also inhibits mitochondrial terminal oxidation and respiration. In addition to these metabolic effects, zinc accumulation exhibits anti-proliferative effects via its induction of mitochondrial apoptogenesis. Zinc accumulation also inhibits the invasive/migration activities in malignant prostate cells. The anti-proliferative effects and the effects on invasion and migration occur through zinc activation of specific intracellular signaling pathways. Consequently, these effects impose anti-tumor actions by zinc. The ability of prostate cells to accumulate zinc is due to the expression and activity of the zinc uptake transporter, ZIP1. To avoid the anti-tumor effects of zinc, in prostate cancer the malignant prostate cells exhibit a silencing of ZIP1 gene expression accompanied by a depletion of cellular zinc. Therefore we regard ZIP1 as a tumor suppressor gene in prostate cancer. In addition to prostate cells, similar tumor suppressor effects of zinc have been identified in several other types of tumors. KeywordsZinc; prostate cancer; tumor suppressor; apoptosis; Krebs cycle; zinc transporter; intermediary metabolismThe physiology and biochemistry of zinc and its importance in normal cellular and bodily function has been the subject of numerous reviews [1][2][3][4]. The regulation and maintenance of a "normal" concentration and distribution of cellular zinc are essential to the function, metabolism, growth, proliferation and survival of cells. A significant clinical aspect of zinc is its role in the development and progression of malignancy. There is now compelling clinical and experimental evidence that zinc is an important factor in prostate cancer, and also in other types of cancer. In relation to essential tumor cell activities, the effects of zinc can be categorized as: intermediary metabolism and bioenergetics effects; motility and invasive effects; growth and proliferation effects. The actions of zinc on all three activities impose antitumor effects in malignant prostate cells and other tumor cells. This review will present the *Correspondence to: Renty B.

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“…Thus, deficits in zinc intake could have a significant impact on the development of cancer. Epidemiological studies have shown decreased zinc status in cancer patients compared with healthy controls (9)(10)(11)(12). It has also been suggested as a contributor to esophageal cancer in humans (9,13).…”

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confidence: 99%

Low intracellular zinc induces oxidative DNA damage, disrupts p53, NFκB, and AP1 DNA binding, and affects DNA repair in a rat glioma cell line

Ames

2002

Proc. Natl. Acad. Sci. U.S.A.

362

269

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Approximately 10% of the U.S. population ingests <50% of the current recommended daily allowance for zinc. We investigate the effect of zinc deficiency on DNA damage, expression of DNA-repair enzymes, and downstream signaling events in a cell-culture model. Low zinc inhibited cell growth of rat glioma C6 cells and increased oxidative stress. Low intracellular zinc increased DNA single-strand breaks (comet assay). Zinc-deficient C6 cells also exhibited an increase in the expression of the zinc-containing DNA-repair proteins p53 and apurinic endonuclease (APE). Repletion with zinc restored cell growth and reversed DNA damage. APE is a multifunctional protein that not only repairs DNA but also controls DNA-binding activity of many transcription factors that may be involved in cancer progression. The ability of the transcription factors p53, nuclear factor B, and activator protein 1 (AP1) to bind to consensus DNA sequences was decreased markedly with zinc deficiency, as assayed by electrophoretic mobility-shift assays. Thus, low intracellular zinc status causes oxidative DNA damage and induces DNA-repair protein expression, but binding of p53 and important downstream signals leading to proper DNA repair are lost without zinc.

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Nutritional and Zinc Status of Head and Neck Cancer Patients: An Interpretive Review

Cited by 80 publications

References 26 publications

Reduction in squamous cell carcinomas in mouse skin by dietary zinc supplementation

Reduction in squamous cell carcinomas in mouse skin by dietary zinc supplementation

Zinc as an anti-tumor agent in prostate cancer and in other cancers

Low intracellular zinc induces oxidative DNA damage, disrupts p53, NFκB, and AP1 DNA binding, and affects DNA repair in a rat glioma cell line

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