Chemopreventive effects of zinc on prostate carcinogenesis induced by N-methyl-N-nitrosourea and testosterone in adult male Sprague-Dawley rats

Banudevi, Sivanantham; Elumalai, Perumal; Ramachandran, A.; Kalimuthu, S; Gunadharini, Dharmalingam Nandagopal; Sharmila, Govindaraj; Arunakaran, J.

doi:10.1007/s00432-010-0926-4

Cited by 22 publications

(16 citation statements)

References 28 publications

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“…6 Experiments using the transgenic adenocarcinoma of the mouse prostate (TRAMP) model also suggest that an ‘optimal’ level of zinc in animal diet (30 ppm) is protective against prostate carcinogenesis. 67 Findings by Banudevi et al 68, 69 document the chemopreventative effects of zinc on prostate carcinogenesis induced by N -methyl- N -nitrosourea and testosterone in the adult male Sprague–Dawley rats. Our own studies provide evidence that hZIP1 transporter overexpression induces regression of prostate tumor growth in a PC3 xenograft mouse model.…”

Section: Experimental Data Versus Epidemiologymentioning

confidence: 98%

Zinc and zinc transporters in prostate carcinogenesis

et al. 2013

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The healthy human prostate accumulates the highest level of zinc of any soft tissue in the body. This unique property is retained in BPH, but is lost in prostatic malignancy, which implicates changes in zinc and its transporters in carcinogenesis. Indeed, zinc concentrations diminish early in the course of prostate carcinogenesis, preceding histopathological changes, and continue to decline during progression toward castration-resistant disease. Numerous studies suggest that increased zinc intake might protect against progression of prostatic malignancy. Despite increased dietary intake, zinc accumulation might be limited by the diminished expression of zinc uptake transporters, resulting in decreased intratumoural zinc levels. This finding can explain the conflicting results of various epidemiological studies evaluating the role of zinc supplementation on primary and secondary prostate cancer prevention. Overall, more research into the mechanisms of zinc homeostasis are needed to fully understand its impact on prostate carcinogenesis. Only then can the potential of zinc and zinc transport proteins be harnessed in the diagnosis and treatment of men with prostate cancer.

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Section: Experimental Data Versus Epidemiologymentioning

confidence: 98%

Zinc and zinc transporters in prostate carcinogenesis

et al. 2013

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“…Deficiency in such a daily dose, leading to a serum zinc(II) concentration is less than 10 μM [119]. Zinc(II) deficiency could disrupt the function of both signaling molecules and proteins directly involved in DNA replication and repair [137][138][139]. Moreover, zinc(II) affect function of anti-tumor gene p53 -as demonstrated in the rat glioma C6 cells -zinc(II) deficiency upregulates expression of p53.…”

Section: Zinc(ii) In Dietmentioning

confidence: 99%

Insight to Physiology and Pathology of Zinc(II) Ions and Their Actions in Breast and Prostate Carcinoma

Gumulec¹,

Masařík²,

Křížková³

et al. 2011

CMC

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Zinc(II) ions contribute to a number of biological processes e.g. DNA synthesis, gene expression, enzymatic catalysis, neurotransmission, and apoptosis. Zinc(II) dysregulation, deficiency and over-supply are connected with various diseases, particularly cancer. 98 % of human body zinc(II) is localized in the intracellular compartment, where zinc(II) is bound with low affinity to metallothionein (MT). Zinc transporters ZIP and ZnT maintain transmembrane transport from/to cells or organelles. Imbalance of their regulation is described in cancers, particularly prostate (down-regulated zinc transporters ZIP1, 2, 3 and ZnT-2) and breast, notably its high-risk variant (up-regulated ZIP6, 7, 10). As a result, intracellular and even blood plasma zinc(II) levels are altered. MT protects cells against oxidative stress, because it cooperates with reduced glutathione (GSH). Recent studies indicate elevated serum level of MT in a number of malignancies, among others in breast, and prostate. MT together with zinc(II) affect apoptosis and proliferation, thus together with its antioxidative effects it may affect cancer. To date, only little is known about the influence of zinc(II) and MT on cancer, while these compounds may play an important role in pathogenesis. This review concludes current data regarding the impact of zinc(II) on the pathogenesis of breast and prostate cancers with potential outlines of new, targeted therapy and prevention. Moreover, blood plasma zinc(II) and MT levels and dietary zinc(II) intake are discussed in relation to breast and prostate cancer risk.

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“…On the other hand, several studies have found that zinc (Zn), a micronutrient involved in structural and regulatory functions in mammalian cells [15], could also be associated with erythrocytes production, hemoglobin [16], and serum testosterone levels [17,18].…”

Section: Introductionmentioning

confidence: 99%

High serum zinc and serum testosterone levels were associated with excessive erythrocytosis in men at high altitudes

et al. 2011

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Chronic mountain sickness (CMS), a lack of adaptation to altitude characterized by excessive erythrocytosis (EE), is a health problem associated with life at high altitude. The erythropoietic process is regulated by both erythropoietin and testosterone. Zinc (Zn) is known to be related with testosterone and hemoglobin levels; meanwhile, nitric oxide was also associated with adaptation to high altitude. The aim of this study was to determine the relationship of hemoglobin and CMS score with serum levels of zinc, total testosterone (TT), calculated free testosterone (cFT), bioavailable testosterone (BAT), hemoglobin, and nitric oxide in men at high altitude with or without EE. Men residing in Lima (150 m) and Cerro de Pasco (4,340 m), Peru, were divided into three groups: (1) low altitude, (2) high altitude without EE (hemoglobin < 21 g/dl), and (3) high altitude with EE (hemoglobin ≥ 21 g/dl). Adjusted multivariable regression models showed that serum testosterone (total or free) and Zn levels were independently correlated with increased hemoglobin levels. Similarly, hemoglobin was positively related with signs/symptoms of CMS; however, both increased the serum Zn and the nitric oxide levels correlated with reduced risk for signs/symptoms of CMS. In conclusion, higher serum testosterone levels and Zn levels were associated with EE, and low scores of signs/symptoms of CMS were associated with higher Zn and nitric oxide levels.

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Chemopreventive effects of zinc on prostate carcinogenesis induced by N-methyl-N-nitrosourea and testosterone in adult male Sprague-Dawley rats

Abstract: This study suggests that zinc may have a beneficial effect against MNU and testosterone-induced prostate carcinogenesis. Thus, it may act as a potential chemopreventive agent in targeting the prostate cancer.

Cited by 22 publications

References 28 publications

Zinc and zinc transporters in prostate carcinogenesis

Zinc and zinc transporters in prostate carcinogenesis

Insight to Physiology and Pathology of Zinc(II) Ions and Their Actions in Breast and Prostate Carcinoma

High serum zinc and serum testosterone levels were associated with excessive erythrocytosis in men at high altitudes

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