The evaluation of biologically important trace metals in liver, kidney and breast tissue

Al-Ebraheem, Alia; Farquharson, Michael J.; Ryan, Elizabeth J.

doi:10.1016/j.apradiso.2008.06.018

Cited by 48 publications

(40 citation statements)

References 13 publications

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“…Danielsen and Steinnes [2] 40 years ago reported a 62% decrease in the concentration of zinc in hepatoma vs. adjacent normal tissue in liver biopsies, which has been confirmed in several reports [3–8]. A cellular decrease in zinc of this magnitude will result in significant changes in cell growth, cell function, and cell metabolism, which are important for the development of malignancy.…”

Section: Introductionmentioning

confidence: 87%

ZIP14 Zinc Transporter Downregulation and Zinc Depletion in the Development and Progression of Hepatocellular Cancer

Franklin

Levy

Zou

et al. 2011

J Gastrointest Canc

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Purpose Hepatocellular cancer (HCC) is a deadly and most rapidly increasing cancer in the USA and worldwide. The etiology and factors involved in development of HCC remain largely unknown. A marked decrease in zinc occurs in HCC. Its role and involvement in HCC has not been identified. We investigated the relationship of cellular zinc changes to the development of malignancy, and the identification of potential zinc transporters associated with the inability of hepatoma cells to accumulate zinc. Methods The detection of relative zinc levels in situ in normal hepatic cells vs. hepatoma was performed on normal and HCC tissue sections. ZIP1, 2, 3, and 14 transporters were identified by immunohistochemistry. Results Intracellular zinc levels are markedly decreased in HCC hepatoma cells vs. normal hepatic cells in early stage and advanced stage malignancy. ZIP14 transporter is localized at the plasma membrane in normal hepatocytes, demonstrating its functioning for uptake and accumulation of zinc. The transporter is absent in the hepatoma cells and its gene expression is downregulated. The change in ZIP14 is concurrent with the decrease in zinc. ZIP1, 2, 3 are not associated with normal hepatocyte uptake of zinc, and HCC zinc depletion. HepG2 cells exhibit ZIP14 transporter. Zinc treatment inhibits their growth. Conclusions ZIP14 downregulation is likely involved in the depletion of zinc in the hepatoma cells in HCC. These events occur early in the development of malignancy possibly to protect the malignant cells from tumor suppressor effects of zinc. This provides new insight into important factors associated with HCC carcinogenesis.

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Section: Introductionmentioning

confidence: 87%

ZIP14 Zinc Transporter Downregulation and Zinc Depletion in the Development and Progression of Hepatocellular Cancer

Franklin

Levy

Zou

et al. 2011

J Gastrointest Canc

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“…Several reports have consistently demonstrated that zinc levels in hepatocellular cancer are markedly decreased (~60% decrease) compared to normal liver tissue [4–10]. We recently found that the hepatoma cells in hepatocellular cancer exhibit a major decrease in zinc compared to the hepatocytes in normal liver [11], which further corroborated other reports of decreased zinc in liver cancer [4–10]. Concurrently with the decrease in zinc, we identified ZIP14 as the functional zinc uptake transporter in the normal hepatocytes, which is downregulated in the hepatoma cells.…”

Section: Are the Prostate Cancer–zinc Relationships Applicable To Othmentioning

confidence: 99%

Cytotoxic/tumor suppressor role of zinc for the treatment of cancer: an enigma and an opportunity

Costello

Franklin

2012

Expert Review of Anticancer Therapy

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A major issue relating to many cancers is the absence of effective chemotherapeutic agents; so that most often untreatable morbidity and death are prevalent once the cancer has been detected and has advanced. The search for efficacious anticancer agents is imperative. One potential agent is zinc, which is decreased in the development of some cancers in order to avoid its cytotoxic/tumor suppressor effects on the malignant cells. This provides the basis and opportunity to employ a treatment regimen that restores elevated zinc levels in the malignant cells and elicits the cytotoxic/tumor suppressor effects of zinc. The enigma is that this approach and expectation has not reached fruition. The question is “why?”. This article provides a discussion of relevant zinc issues that need to be considered and resolved. Important areas of research are identified as being essential for the successful application of zinc cytotoxicity/tumor suppression actions for the treatment of specific cancers.

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“…Beginning with Danielsen and Steinnis in 1970, 3 ten reported population studies [3][4][5][6][7][8][9][10][11][12] have consistently demonstrated a marked decrease (~55-75%) in zinc levels in HCC tissue compared with normal liver tissue. The "typical" results are represented in Figure 1 from Kew and Mallet, 7 who concluded that "the zinc concentration in the liver cancer tissue was significantly less than that in the non-cancerous tissues, whether cirrhotic or non-cirrhotic in the HCC patients or normal from the noncancerous patients (P < 0.001 in each instance)."…”

Section: The Status Of Zinc Levels In Hccmentioning

confidence: 99%

The status of zinc in the development of hepatocellular cancer

Costello

Franklin

2014

Cancer Biology & Therapy

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The evaluation of biologically important trace metals in liver, kidney and breast tissue

Cited by 48 publications

References 13 publications

ZIP14 Zinc Transporter Downregulation and Zinc Depletion in the Development and Progression of Hepatocellular Cancer

ZIP14 Zinc Transporter Downregulation and Zinc Depletion in the Development and Progression of Hepatocellular Cancer

Cytotoxic/tumor suppressor role of zinc for the treatment of cancer: an enigma and an opportunity

The status of zinc in the development of hepatocellular cancer

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