Protection of CDC25 phosphatases against oxidative stress in breast cancer cells: Evaluation of the implication of the thioredoxin system

• Published in: Free radical research 2012-05, Vol.46 (5), p.674-689
• Main Authors: Beillerot, Adeline, Battaglia, Eric, Bennasroune, Aline, Bagrel, Denyse
• Format: Article
• Language: English
• Subjects: acrolein; Acrolein - pharmacology; auranofin; Auranofin - pharmacology; Breast Neoplasms - enzymology; Breast Neoplasms - metabolism; cdc25 Phosphatases - antagonists & inhibitors; cdc25 Phosphatases - metabolism; cell cycle; Cell Cycle Checkpoints - drug effects; Cell Line, Tumor; Female; Humans; hydrogen peroxide; Hydrogen Peroxide - pharmacology; oxidative regulation; Oxidative Stress; Reactive Oxygen Species - metabolism; Thioredoxin-Disulfide Reductase - antagonists & inhibitors; Thioredoxin-Disulfide Reductase - metabolism; Thioredoxins - biosynthesis; Thioredoxins - metabolism
• ISSN: 1071-5762; 1029-2470
• DOI: 10.3109/10715762.2012.669039

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.