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Review
. 2009 Apr 1;106(5):750-7.
doi: 10.1002/jcb.22049.

The important role of the apoptotic effects of zinc in the development of cancers

Renty B Franklin  1 , Leslie C Costello
Affiliations
Review

The important role of the apoptotic effects of zinc in the development of cancers

Renty B Franklin et al. J Cell Biochem. .

Abstract

Zinc is a trace element that is essential for the normal function of cells. It is a cofactor for the structure and function of a wide range of cellular proteins including enzymes, transcription factors, and structural proteins. Recent studies have shown that zinc plays a role in the development of various cancers. Unfortunately no established common relationships of zinc with cancer development and progression have been identified. Zinc is known to have systemic effects such as regulation of the immune system as well as direct cellular effects resulting in regulation of gene expression, bioenergetics, metabolic pathways, signal transduction and cell invasion. Zinc is also reported to regulate cell proliferation and growth. In this review presentation we focus on the effects of zinc that are involved in the regulation of apoptosis in malignant cells. We selected the apoptotic effects of zinc because zinc is reported to both induce apoptosis in some cancers and to protect other cancer cells against apoptosis induced by other factors. The effects of zinc in the regulation of apoptosis appear to be cell type specific. More importantly the reported effects of zinc on cancer cells must be viewed from the perspective of the physiological regulation of zinc homeostasis. Thus one must be mindful of the experimental conditions under which zinc effects are investigated relative to the physiological and pathological conditions of cellular zinc distribution and concentrations that can exist in situ.

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Figures

Figure 1
Figure 1
Representation of some zinc-induced apoptotic pathways. A. Direct effects on nucleus. B. Direct effects on mitochondria. C. Direct effect on apoptotic signaling pathways f1,f2,f3. C1/C2. Apoptotic signaling pathway effects on nucleus or mitochondria. D. Effects of mitochondrial factors on nucleus. E1/E2. Effects of mitochondrial factors mediated through the apoptotic signaling pathway.
Figure 2
Figure 2
The concept of the genetic/metabolic transformation in the development of malignant cells.
Figure 3
Figure 3
The role of Zip1 and zinc in the genetic/metabolic transformation of normal prostate cells to malignant cells.
Figure 4
Figure 4
Zinc induction of apoptogenesis in prostate cells. 1. Cytosolic zinc directly interacts with mitochondrial resident Bax to facilitate pore formation and release of cytochrome c for caspase activation leading to apoptosis. 2. Cytosolic zinc facilitates the insertion of cytosolic Bax into the mitochondrial membrane. Cytosolic zinc activates Bax gene-associated transcription factor, which increases expression and cellular level of Bax.
See this image and copyright information in PMC

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