Direct effect of zinc on mitochondrial apoptogenesis in prostate cells

Abstract

Exposure to zinc induces apoptosis in PC-3 and BPH cells, which accumulate high intracellular levels of zinc, but not in HPR-1 cells, which do not accumulate high levels of zinc. Once initiated, the induction of apoptosis is not reversed by the removal of zinc, i.e., it is an irreversible process. The apoptogenic effect is due to a direct effect of zinc on mitochondria that results in the release of cytochrome c. The cell specificity of zinc induction of apoptogenesis is dependent on the ability of the cells to accumulate high levels of intracellular zinc and on the ability of the mitochondria to respond to the direct effect of zinc.

Role of zinc in the pathogenesis and treatment of prostate cancer: critical issues to resolve

“…One such effect is the inhibition of cell growth, which results from its induction of mitochondrial apoptogenesis. [7][8][9] This effect has been identified in human prostate cell lines (PC-3, LNCaP, BPH-1) and in normal rat ventral prostate epithelium, all of which are capable of accumulating high zinc levels when exposed to zinc-supplemented medium. In contrast, the human prostate HPr-1 cell line and the squamous carcinoma cell line, which are not zincaccumulating cells, do not exhibit an apoptogenic response to zinc treatment.…”

Mitochondrial function, zinc, and intermediary metabolism relationships in normal prostate and prostate cancer

“…This effect results from a direct action of zinc on the mitochondrial release of cytochrome c followed by caspase activation and cascading apoptotic events (Feng et al, 2000(Feng et al, , 2002. Although the mechanism of this effect needs to be elucidated, our recent studies (unpublished) reveal that cytosolic zinc directly interacts with the mitochondria to facilitate Bax pore-forming activity (Fig.…”

“…A consequence of the cellular accumulation of zinc is an inhibitory effect on proliferation of these prostate cells that results from its induction of apoptosis (Liang et al, 1999;Feng et al, 2000). This effect results from a direct action of zinc on the mitochondrial release of cytochrome c followed by caspase activation and cascading apoptotic events (Feng et al, 2000(Feng et al, , 2002.…”

Decreased zinc and downregulation of ZIP3 zinc uptake transporter in the development of pancreatic adenocarcinoma

“…[2][3][4] These include: altered bioenergetic/metabolic effects; 2 growth-inhibitory/apoptogenic effects; [17][18][19][20][21][22][23] and cell motility/invasive inhibitory effects. [24][25][26] The depletion of zinc is an essential event to protect the malignant cells from the tumor suppressor effects of zinc.…”