Zinc induces mitochondria apoptogenesis in prostate cells

Background and Purpose: Prostate secretory epithelial cells have the unique function and capability of accumulating extremely high intracellular level s of zinc. One of the effects of this accumulation is inhibition of cell gr owth due, in part, to an increase in apoptosis, The present studies were co nducted to determine if this zinc-induced apoptosis involves stimulation of mitochondrial apoptogenesis. Materials and Methods: The PC-3 a human malignant prostate cell line, which is zinc accumulating, was exposed to medium supplemented with physiologic levels of zinc. Results: By 24 h, zinc treatment resulted in the translocation of cytochrom e c from the mitochondria to the cytosol, the activation of caspase-9 and c aspase-3, and eventually, the cleavage of nuclear poly(ADP)-ribose polymera se (PARP), Under similar conditions, exposure of freshly prepared rat ventr al prostate cells (which are also zinc accumulating) resulted in increased apoptosis following translocation of cyochrome c and activation of caspases -9 and 3, The human prostate PZ-HPV-7 cells, which do not accumulate zinc, did not exhibit any apoptotic effect from zinc treatment. Conclusion: The accumulation of high intracellular levels of zinc by prosta te cells induces mitochondrial apoptogenesis, This represents a newly ident ified physiological effect of zinc in the regulation of prostate cell growt h.