The status of zinc in the development of hepatocellular cancer

Abstract

Liver cancer (hepatocellular carcinoma, HCC) is increasing worldwide. About 75% of HCC cases result in death generally within one year. The factors responsible for the initiation and progression of HCC remain largely unknown and speculative, thereby impeding advancements in the development of effective therapeutic agents and biomarkers for early detection of HCC. A consistent marked decrease in zinc in HCC tumors compared with normal liver is an established clinical relationship, which occurs in virtually all cases of HCC. However, this relationship has been largely ignored by the contemporary clinical and research community. Consequently, the factors and mechanisms involved in this relationship have not been addressed. Thus, the opportunity and potential for its employment as biomarkers for early identification of malignancy, and for development of a chemotherapeutic approach have been lacking. This presentation includes a review of the literature and the description of important recent and new data, which provide the basis for a concept of the role of zinc in the development of HCC. The basis is presented for characterizing HCC malignancy as ZIP14-deficient tumors, and its requirement to prevent zinc cytotoxic effects on the malignant cells. The potential for an efficacious zinc treatment approach for HCC is described. The involvement of zinc in the predisposition for HCC by chronic liver disease/cirrhosis is presented. Hopefully, this presentation will raise the awareness, interest, and support for the much needed research in the implications of zinc in the development and progression of HCC.

Keywords: :

• ZIP14
• cirrhosis
• hepatocellular carcinoma
• hepatocytes
• hepatoma cells
• tumor suppression
• zinc

10.4161/cbt.27633

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

The studies of the authors (L.C.C. and R.B.F.) cited and described in this review were supported by NIH grants CA79903, CA93443, and DK42839.