title: Protection of CDC25 phosphatases against oxidative stress in breast cancer cells: evaluation of the implication of the thioredoxin system.
abstract: Reactive oxygen species regulate protein functionality. Cell cycle CDC25 phosphatases are targets of such oxidative regulation in vitro. We sought to evaluate if a thioredoxin (trx)-dependent redox regulation of CDC25 exists in cancer cells. For that purpose, we used MCF7 and MDA-MB 231 breast cancer cells, which express trx1 differentially, together with two trx/thioredoxin reductase (trxR) inhibitors, Auranofin and Acrolein. Auranofin could induce a full trxR inhibition associated with ROS production in both cell lines. Acrolein could provoke similar effects only in MDA-MB 231 cells with a low trx1 expression. Simultaneous trx1 oxidation and trxR inactivation occurred only in the presence of Acrolein and resulted in a G2-M cell cycle arrest, without full CDC25 inhibition in MDA-MB 231 cells. Our data suggest that the maintenance of CDC25 activity does not fully rely on the trx system in breast cancer cells, even in the presence of a major oxidative stress.
authors.affiliation: Laboratoire d'Ingénierie Moléculaire et Biochimie Pharmacologique, Université de Lorraine, Metz, France.
authors.forename: Adeline
authors.initials: A
authors.lastname: Beillerot
authors.forename: Eric
authors.initials: E
authors.lastname: Battaglia
authors.forename: Aline
authors.initials: A
authors.lastname: Bennasroune
authors.forename: Denyse
authors.initials: D
authors.lastname: Bagrel
mesh_terms: D000171:Acrolein / Q000494:pharmacology; D001310:Auranofin / Q000494:pharmacology; D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D013880:Thioredoxin-Disulfide Reductase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013879:Thioredoxins / Q000096:biosynthesis* / Q000378:metabolism; D020687:cdc25 Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D001310:Auranofin; D013879:Thioredoxins; D000171:Acrolein; D006861:Hydrogen Peroxide; D013880:Thioredoxin-Disulfide Reductase; D020687:cdc25 Phosphatases