INDUCTION OF NECROSIS BY ZINC IN PROSTATE CARCINOMA-CELLS AND IDENTIFICATION OF PROTEINS INCREASED IN ASSOCIATION WITH THIS INDUCTION

Zinc exhibits inhibitory effects on apoptosis, and a deficiency in thi s metal generally causes this type of cell death to occur. In the pres ent study, we found that exposure to zinc results in necrosis of prost ate carcinoma cells. When zinc acetate was added to LNCaP or PC-3 cell s in monolayer culture, they began to detach from the culture dishes, and viability was lost after 4-8 h. Most of the cell death was found t o be due to necrosis as determined by double staining with fluorescein -isothiocyanate-labeled annexin V and ethidium bromide, and by detecti on of hypodiploid cells. Associated with the induction of necrosis was an increase in low molecular-mass proteins, identified by HPLC analys is to be thymosin beta 10, parathymosin and GAGE in LNCaP cells, and t hymosin beta 4, parathymosin and metallothionein in PC-3. The time cou rse of the increase of thymosin beta 10 in LNCaP cells and thymosin be ta 4 in PC-3 cells was consistent with that of appearance of cell deta chment and dead cells. These results indicate that zinc can induce nec rosis and suggest that production of proteins including beta-thymosins is involved in induction of processes leading to cell detachment.