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: Adeline Beillerot, Eric Battaglia, Aline Bennasroune, Denyse Bagrel
• Journal: Free radical research (Free Radic Res) Vol. 46 Issue 5 Pg. 674-89 (May 2012) ISSN: 1029-2470 [Electronic] England
• PMID: 22360685 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Reactive Oxygen Species
• Auranofin
• Thioredoxins
• Acrolein
• Hydrogen Peroxide
• Thioredoxin-Disulfide Reductase
• cdc25 Phosphatases

Topics

• Acrolein (pharmacology)
• Auranofin (pharmacology)
• Breast Neoplasms (enzymology, metabolism)
• Cell Cycle Checkpoints (drug effects)
• Cell Line, Tumor
• Female
• Humans
• Hydrogen Peroxide (pharmacology)
• Oxidative Stress
• Reactive Oxygen Species (metabolism)
• Thioredoxin-Disulfide Reductase (antagonists & inhibitors, metabolism)
• Thioredoxins (biosynthesis, metabolism)
• cdc25 Phosphatases (antagonists & inhibitors, metabolism)