Zinc in Cancer Prevention

Essentiality of zinc for humans was discovered 45 yr ago. Deficiency of zinc is prevalent world wide in developing countries and may affect nearly 2 billion subjects. The major manifestations of zinc deficiency include growth retardation, hypogonadism in males, cell-mediated immune dysfunctions, and cognitive impairment. Zinc not only improves cell mediated immune functions but also functions as an antioxidant and anti-inflammatory agent. Oxidative stress and chronic inflammation have been implicated in development of many cancers. In patients with head and neck cancer, we have shown that nearly 65% of these patients were zinc deficient based on their cellular zinc concentrations. Natural killer (NK) cell activity and IL-2 generation were also affected adversely. Th2 cytokines were not affected. In our patients, zinc status was a better indicator of tumor burden and stage of disease in comparison to the overall nutritional status. Zinc status also correlated with number of hospital admissions and incidences of infections. NF-κ B is constitutively activated in many cancer cells, and this results in activation of antiapoptotic genes, VEGF, cyclin DI, EGFR, MMP-9 and inflammatory cytokines. Zinc inhibits NF-κ B via induction of A-20. Thus, zinc supplementation should have beneficial effects on cancer by decreasing angiogenesis and induction of inflammatory cytokines while increasing apoptosis in cancer cells. Based on the above, we recommend further studies and propose that zinc should be utilized in the management and chemoprevention of cancer.

[1]  B. Bao,et al.  Zinc enhances the expression of interleukin-2 and interleukin-2 receptors in HUT-78 cells by way of NF-kappaB activation. , 2002, The Journal of laboratory and clinical medicine.

[2]  J. Farber,et al.  Esophageal cancer prevention in zinc-deficient rats: rapid induction of apoptosis by replenishing zinc. , 2001, Journal of the National Cancer Institute.

[3]  F. Sarkar,et al.  Soy isoflavone supplementation in healthy men prevents NF-κB activation by TNF-α in blood lymphocytes , 2001 .

[4]  A. Prasad,et al.  Serum thymulin in human zinc deficiency. , 1988, The Journal of clinical investigation.

[5]  W. Goodwin,et al.  The value of the prognostic nutritional index in the management of patients with advanced carcinoma of the head and neck. , 1984, Head & neck surgery.

[6]  A S Prasad,et al.  Zinc and immune function: the biological basis of altered resistance to infection. , 1998, The American journal of clinical nutrition.

[7]  M. Iskra,et al.  Analysis of serum copper and zinc concentrations in cancer patients , 2007, Biological Trace Element Research.

[8]  R. Beyaert,et al.  The cytokine‐inducible zinc finger protein A20 inhibits IL‐1‐induced NF‐κB activation at the level of TRAF6 , 1999, FEBS letters.

[9]  P. Lachance,et al.  Antioxidants: an integrative approach. , 2001, Nutrition.

[10]  T. Clemons,et al.  Associations of mortality with ocular disorders and an intervention of high-dose antioxidants and zinc in the Age-Related Eye Disease Study: AREDS Report No. 13. , 2004, Archives of ophthalmology.

[11]  J. Shiloach,et al.  Zinc-binding of endostatin is essential for its antiangiogenic activity. , 1998, Biochemical and biophysical research communications.

[12]  M S Boguski,et al.  The A20 cDNA induced by tumor necrosis factor alpha encodes a novel type of zinc finger protein. , 1990, The Journal of biological chemistry.

[13]  A. Prasad,et al.  Human zinc deficiency, endocrine manifestations and response to treatment. , 1967, American Journal of Clinical Nutrition.

[14]  A. Prasad,et al.  Zinc metabolism in patients with the syndrome of iron deficiency anemia, hepatosplenomegaly, dwarfism, and hypognadism. , 1963, The Journal of laboratory and clinical medicine.

[15]  Bin Bao,et al.  Antioxidant effect of zinc in humans. , 2004, Free radical biology & medicine.

[16]  B. Bao,et al.  Zinc activates NF-κB in HUT-78 cells , 2001 .

[17]  R. Black,et al.  Zinc supplementation in young children with acute diarrhea in India. , 1995, The New England journal of medicine.

[18]  A. Prasad,et al.  Syndrome of iron deficiency anemia, hepatosplenomegaly, hypogonadism, dwarfism and geophagia. , 2009, Transactions of the American Clinical and Climatological Association.

[19]  F. Beck,et al.  Nutritional and zinc status of head and neck cancer patients: an interpretive review. , 1998, Journal of the American College of Nutrition.

[20]  A. Prasad Zinc in human health: An update , 1998 .

[21]  R. Uzzo,et al.  Zinc inhibits nuclear factor-kappa B activation and sensitizes prostate cancer cells to cytotoxic agents. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[22]  A. Krikos,et al.  Transcriptional activation of the tumor necrosis factor alpha-inducible zinc finger protein, A20, is mediated by kappa B elements. , 1992, The Journal of biological chemistry.

[23]  E. B. Hart,et al.  Zinc in the Nutrition of the Rat , 2009 .

[24]  F. Beck,et al.  Changes in cytokine production and T cell subpopulations in experimentally induced zinc-deficient humans. , 1997, The American journal of physiology.

[25]  A. Prasad Effects of zinc deficiency on Th1 and Th2 cytokine shifts. , 2000, The Journal of infectious diseases.

[26]  Joseph R. Bertino,et al.  Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group. , 1980, The American journal of medicine.

[27]  H. Levine,et al.  Predicting Postoperative Head and Neck Complications Using Nutritional Assessment: The Prognostic Nutritional Index , 1983 .

[28]  E. Ho,et al.  Dietary Zinc Supplementation Inhibits NFκB Activation and Protects Against Chemically Induced Diabetes in CD1 Mice , 2001, Experimental biology and medicine.

[29]  F. Beck,et al.  Effect of zinc supplementation on incidence of infections and hospital admissions in sickle cell disease (SCD) , 1999, American journal of hematology.

[30]  A. Prasad Clinical, immunological, anti-inflammatory and antioxidant roles of zinc , 2008, Experimental Gerontology.

[31]  R. Black,et al.  Zinc Supplementation Reduces the Incidence of Acute Lower Respiratory Infections in Infants and Preschool Children: A Double-blind, Controlled Trial , 1998, Pediatrics.

[32]  Jennifer I. Lim,et al.  A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. , 2001, Archives of ophthalmology.

[33]  J. Larrick,et al.  Enhancement of neutrophil superoxide production by preincubation with recombinant human tumor necrosis factor. , 1987, Journal of immunology.

[34]  A. Prasad,et al.  Effects of zinc and nutritional status on clinical outcomes in head and neck cancer. , 1998, Nutrition.

[35]  J. Riordan Biochemistry of zinc. , 1976, The Medical clinics of North America.

[36]  G. Brookes Nutritional Status-a Prognostic Indicator in Head and Neck Cancer , 1985, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[37]  B. Freeman,et al.  Reactive oxygen species in human health and disease. , 2001, Nutrition.

[38]  Bin Bao,et al.  Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress. , 2007, The American journal of clinical nutrition.