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 levels of zinc. One of the effects of this accumulation is inhibition of cell growth due, in part, to an increase in apoptosis. The present studies were conducted 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 cytochrome c from the mitochondria to the cytosol, the activation of caspase-9 and caspase-3, and eventually, the cleavage of nuclear poly(ADP)-ribose polymerase (PARP). Under similar conditions, exposure of freshly prepared rat ventral prostate cells (which are also zinc accumulating) resulted in increased apoptosis following translocation of cytochrome 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 prostate cells induces mitochondrial apoptogenesis. This represents a newly identified physiological effect of zinc in the regulation of prostate cell growth.