title: Inhibition by zinc of deoxycholate-induced apoptosis in HCT-116 cells.
abstract: The bile acid, deoxycholate, can induce apoptosis although the effect of trace elements on such cell death is unknown. The aim of this study was to determine if deoxycholate-induced apoptosis is influenced by zinc. HCT-116 colon epithelial cells were pre-treated with zinc and then exposed to deoxycholate. Membrane blebbing, formation of apoptotic bodies, and greater overall production of reactive oxygen species (ROS) occurred in cells exposed to deoxycholate, but zinc inhibited the occurrence of these three events caused by deoxycholate. Upon finer analysis, stimulation of mitochondrial superoxide production, mitochondrial dysfunction, and cytochrome c release were detected in cells exposed to deoxycholate, but zinc did not inhibit any of these three effects caused by deoxycholate. Additionally, caspase-3 activation, plasma membrane phospholipid translocation, and also chromatin condensation and fragmentation were observed in cells exposed to deoxycholate, but all of these effects of deoxycholate, including the greater overall ROS production, were all inhibited by zinc. Because zinc did not prevent the three mitochondrial effects caused by deoxycholate, the last set of findings suggested that zinc hampered activation of an initiator caspase upstream of effector caspase-3, in inhibiting deoxycholate-induced HCT-116 cell death. In examining this possibility, it was found that caspase-8 activation caused by deoxycholate was blocked by zinc. Collectively, the results suggest that zinc can inhibit deoxycholate-induced apoptotic cell death mediated by caspases.
authors: Cellular and Molecular Nutrition Research Laboratory, Department of Nutrition, University of North Carolina at Greensboro, Greensboro, North Carolina 27412, USA.
authors: Abigail F
authors: AF
authors: Smith
authors: Jennifer
authors: J
authors: Longpre
authors: George
authors: G
authors: Loo
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D019610:Cytoprotection; D053938:DNA Fragmentation / Q000187:drug effects; D003840:Deoxycholic Acid / Q000494:pharmacology*; D045325:HCT116 Cells; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009153:Mutagens / Q000494:pharmacology*; D010743:Phospholipids / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D015032:Zinc / Q000494:pharmacology*
chemical_list: D009153:Mutagens; D010743:Phospholipids; D003840:Deoxycholic Acid; D013481:Superoxides; D045304:Cytochromes c; C505407:CASP3 protein, human; C505530:CASP8 protein, human; D053148:Caspase 3; D053181:Caspase 8; D015032:Zinc