Cytotoxic Effects of Manganese in Human Prostate Carcinoma DU145 Cells

Abstract

Manganese (Mn) is a micro‐nutrient essential for maintaining the normal functions of many enzymes and other proteins in mammalian cells and tissues. However, Mn is toxic when taken in excess. Our previous studies have shown that Mn induces cell death in human neural tumor cells by altering, in part, their energy metabolism leading to necrosis. To investigate the hypothesis that Mn generally exerts toxicity in cancer cells by inducing them to undergo apoptosis and/or necrosis, this study aims to determine the effects of Mn on human prostate carcinoma DU145 cells. Our results demonstrate that at pathophysiological levels Mn induced dose‐related decrease in survival of DU145 cells concomitant with alterations in their cellular morphology. Results from flow cytometry analysis and lactate dehydrogenase release assays obtained with DU145 cells treated with MnCl2 for 48 hours revealed that at lower treatment levels, Mn induced mainly apoptosis whereas at higher levels, it induced mainly necrosis in DU145 cells. Studies are ongoing to determine the signaling mechanisms underlying the Mn‐mediated effects. Thus, our findings may assume pathophysiological significance of Mn toxicity in prostate cancer and may have implications in cancer chemotherapy.